subject:(Podocyte)

University of Gothenburg / Göteborgs Universitet

1. Bergwall, Lovisa. A Podocyte view on RhoGTPases and actin cytoskeleton regulation.

Degree: 2020, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/64541

► Proteinuria is a hallmark symptom of chronic kidney disease, that if left to persist constitutes a risk for progression of disease. Symptomatic treatment aiming at… (more)

▼ Proteinuria is a hallmark symptom of chronic kidney disease, that if left to persist constitutes a risk for progression of disease. Symptomatic treatment aiming at decreasing proteinuria is therefore standard practice. Curative treatments for the underlying cause of disease are however lacking and treatments currently in use to induce disease remission are associated with unfavorable side effects. Dysregulation of the podocyte actin cytoskeleton underlies the pathological process called foot process effacement (FPE), which is one of the leading causes of proteinuria. The studies included in this thesis have focused on podocyte actin cytoskeleton regulation and a group of proteins called RhoGTPases, known to be involved in actin cytoskeleton regulation in podocytes. In the first study, glomerular microarray analysis showed an increase in the expression of the melanocortin 1-receptor (MC1R) in renal diseases focal segmental glomerulosclerosis and membranous nephropathy. Subsequent mass spectrometry analysis in combination with pathway and biochemical analysis revealed the podocyte protective effects of MC1R stimulation in vitro. Activation of MC1R proved to be stabilizing the podocyte actin cytoskeleton through inhibition of the epidermal growth factor receptor (EGFR) and maintenance of the actin associated protein synaptopodin. In the second study, the depletion of the prenylation enzyme Geranylgeranyl transferase type I (GGTase-I) in podocytes led to the development of proteinuria and FPE in mice due to an imbalanced RhoGTPase activity and disruption of the actin cytoskeleton. These findings suggest that GGTase-I activity is essential for podocyte function. In the last study, a guanine nucleotide exchange factor (activator of RhoGTPases) named Bpix was identified to be modulated in podocytes following treatment with a renal stressor, using mass spectrometry analysis. Gene silencing of Bpix protected against actin cytoskeleton remodulation in a model of podocyte injury, demonstrating the importance of Bpix for podocyte actin cytoskeleton regulation. In conclusion, the results in this thesis confirm the importance of actin cytoskeleton regulation for podocyte integrity. Further on, the results provide new information on actin cytoskeleton regulatory pathways involving RhoGTPases in podocytes, which can be of importance for future attempts in finding targeted treatments of proteinuria and chronic kidney disease.

Subjects/Keywords: Podocyte; RhoGTPases; Actin cytoskeleton regulation

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APA (6^th Edition):

Bergwall, L. (2020). A Podocyte view on RhoGTPases and actin cytoskeleton regulation. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/64541

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bergwall, Lovisa. “A Podocyte view on RhoGTPases and actin cytoskeleton regulation.” 2020. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed February 27, 2021. http://hdl.handle.net/2077/64541.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bergwall, Lovisa. “A Podocyte view on RhoGTPases and actin cytoskeleton regulation.” 2020. Web. 27 Feb 2021.

Vancouver:

Bergwall L. A Podocyte view on RhoGTPases and actin cytoskeleton regulation. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2020. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/2077/64541.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bergwall L. A Podocyte view on RhoGTPases and actin cytoskeleton regulation. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2020. Available from: http://hdl.handle.net/2077/64541

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. Yamazaki, Mihoko. Possible role for glomerular-derived angiotensinogen in nephrotic syndrome. : ネフローゼ症候群における糸球体由来アンジオテンシノーゲンの役割.

Degree: 博士（医学）, 2017, Niigata University / 新潟大学

URL: http://hdl.handle.net/10191/47593

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学位の種類: 博士（医学）. 報告番号: 甲第4262号. 学位記番号: 新大院博（医）甲第740号. 学位授与年月日: 平成29年3月23日

Journal of the Renin-Angiotensin-Aldosterone System 17(4),2016

Background and objective: Renin-angiotensin system (RAS) inhibitors reduce glomerular injury and… (more)

Subjects/Keywords: Angiotensinogen; podocyte; slit diaphragm; nephrin

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APA (6^th Edition):

Yamazaki, M. (2017). Possible role for glomerular-derived angiotensinogen in nephrotic syndrome. : ネフローゼ症候群における糸球体由来アンジオテンシノーゲンの役割. (Thesis). Niigata University / 新潟大学. Retrieved from http://hdl.handle.net/10191/47593

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yamazaki, Mihoko. “Possible role for glomerular-derived angiotensinogen in nephrotic syndrome. : ネフローゼ症候群における糸球体由来アンジオテンシノーゲンの役割.” 2017. Thesis, Niigata University / 新潟大学. Accessed February 27, 2021. http://hdl.handle.net/10191/47593.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yamazaki, Mihoko. “Possible role for glomerular-derived angiotensinogen in nephrotic syndrome. : ネフローゼ症候群における糸球体由来アンジオテンシノーゲンの役割.” 2017. Web. 27 Feb 2021.

Vancouver:

Yamazaki M. Possible role for glomerular-derived angiotensinogen in nephrotic syndrome. : ネフローゼ症候群における糸球体由来アンジオテンシノーゲンの役割. [Internet] [Thesis]. Niigata University / 新潟大学; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10191/47593.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yamazaki M. Possible role for glomerular-derived angiotensinogen in nephrotic syndrome. : ネフローゼ症候群における糸球体由来アンジオテンシノーゲンの役割. [Thesis]. Niigata University / 新潟大学; 2017. Available from: http://hdl.handle.net/10191/47593

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Guelph

3. Mahesaniya, Afreeda. Investigating the effects of soy phytoestrogens on Nephrin and Akt podocyte survival signaling pathway.

Degree: MS, Department of Molecular and Cellular Biology, 2017, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/11603

► Chronic kidney disease (CKD) is a debilitating illness which is increasing in frequency in the Canadian population as a consequence of the diabetes epidemic. Physicians… (more)

▼ Chronic kidney disease (CKD) is a debilitating illness which is increasing in frequency in the Canadian population as a consequence of the diabetes epidemic. Physicians and patients are becoming increasingly interested in using lifestyle modifications to supplement treatment and improve clinical outcomes. Anecdotal evidence suggests that a soy-based diet, which consists of phytoestrogens – daidzein and genistein, can decrease proteinuria in CKD patients, although the molecular mechanisms behind this phenomenon remain unknown. The ability of the kidneys to properly filter blood is vitally dependent on specialized, terminally differentiated cells known as podocytes, loss of which results in altered filtration selectivity. Podocytes extend foot processes, which are bridged by the slit diaphragm (SD), a specialized intercellular junction. Perturbations in nephrin, a major SD protein, compromise podocyte survival and ultimately filtration function. Nephrin elicits signaling via phosphorylation of tyrosine residues on its cytoplasmic tail, leading to recruitment and activation of proteins including the survival signaling protein Akt. We have now shown that nephrin/Akt signaling is enhanced in mice following feeding of a soy-based diet. Intriguingly, this observation is more pronounced in female compared to male mice, implicating that sex-specific differences, such as those imposed by the estrogen receptor (ER), may play an important role in this response. Accordingly, soy supplementation induces activation of Akt, which is a known target of the activated ER and a key regulator of podocyte survival. Using cultured podocytes, we further demonstrate that treatment with daidzein promotes podocyte protection following high glucose exposure. Altogether, this work provides mechanistic insight to support the renoprotective effects of soy and its sex-specific effects on kidney function, in addition to identifying an optimal dosage and duration of soy supplementation in mice which is clinically applicable. Advisors/Committee Members: Jones, Nina (advisor).

Subjects/Keywords: Soy; phytoestrogens; Akt; Podocyte; Nephrin

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APA (6^th Edition):

Mahesaniya, A. (2017). Investigating the effects of soy phytoestrogens on Nephrin and Akt podocyte survival signaling pathway. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/11603

Chicago Manual of Style (16^th Edition):

Mahesaniya, Afreeda. “Investigating the effects of soy phytoestrogens on Nephrin and Akt podocyte survival signaling pathway.” 2017. Masters Thesis, University of Guelph. Accessed February 27, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/11603.

MLA Handbook (7^th Edition):

Mahesaniya, Afreeda. “Investigating the effects of soy phytoestrogens on Nephrin and Akt podocyte survival signaling pathway.” 2017. Web. 27 Feb 2021.

Vancouver:

Mahesaniya A. Investigating the effects of soy phytoestrogens on Nephrin and Akt podocyte survival signaling pathway. [Internet] [Masters thesis]. University of Guelph; 2017. [cited 2021 Feb 27]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/11603.

Council of Science Editors:

Mahesaniya A. Investigating the effects of soy phytoestrogens on Nephrin and Akt podocyte survival signaling pathway. [Masters Thesis]. University of Guelph; 2017. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/11603

University of Guelph

4. Dutta, Nikkita. Investigation of Dok1 and Dok2 as novel modulators of focal adhesion dynamics in kidney podocytes.

Degree: MS, Department of Molecular and Cellular Biology, 2019, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/15994

► Podocyte adhesion to the underlying glomerular basement membrane is required for proper filtration and is mediated by dynamic signalling events. Integrins are a major component… (more)

Subjects/Keywords: Signaling; Podocyte; Adhesion; Dok; Kidney

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dutta, N. (2019). Investigation of Dok1 and Dok2 as novel modulators of focal adhesion dynamics in kidney podocytes. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/15994

Chicago Manual of Style (16^th Edition):

Dutta, Nikkita. “Investigation of Dok1 and Dok2 as novel modulators of focal adhesion dynamics in kidney podocytes.” 2019. Masters Thesis, University of Guelph. Accessed February 27, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/15994.

MLA Handbook (7^th Edition):

Dutta, Nikkita. “Investigation of Dok1 and Dok2 as novel modulators of focal adhesion dynamics in kidney podocytes.” 2019. Web. 27 Feb 2021.

Vancouver:

Dutta N. Investigation of Dok1 and Dok2 as novel modulators of focal adhesion dynamics in kidney podocytes. [Internet] [Masters thesis]. University of Guelph; 2019. [cited 2021 Feb 27]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/15994.

Council of Science Editors:

Dutta N. Investigation of Dok1 and Dok2 as novel modulators of focal adhesion dynamics in kidney podocytes. [Masters Thesis]. University of Guelph; 2019. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/15994

University of Manchester

5. Mccaffrey, James. Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome.

Degree: 2016, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:294549

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BACKGROUND: Nephrotic syndrome (NS) occurs when the glomerular filtration barrier becomes abnormally permeable, leading to the clinical triad of proteinuria, massive oedema, and hypoalbuminaemia. Historically,… (more)

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BACKGROUND: Nephrotic syndrome (NS) occurs when the glomerular filtration barrier becomes abnormally permeable, leading to the clinical triad of proteinuria, massive oedema, and hypoalbuminaemia. Historically, NS has been thought to result from dysregulation of the immune system, although recent evidence suggests the glomerular podocyte plays a central role in disease pathogenesis. Children with NS are generally treated with an empiric course of glucocorticoid (Gc) therapy; a class of steroids which are activating ligands for the glucocorticoid receptor (GR) transcription factor. A major factor limiting the clinical utility of these agents is the marked variation observed in response to treatment. Although Gc-therapy has been the cornerstone of NS management for several decades, the mechanism of action, and target cell, remain poorly understood.HYPOTHESIS AND AIMS: The central hypothesis for this thesis states that glucocorticoids act directly on the podocyte to produce clinically useful effects without involvement of the immune system. FINDINGS: Using a wild-type human podocyte cell line, I demonstrated that the basic GR-signalling mechanism is intact in the podocyte, and that glucocorticoids produce a direct, protective effect on the podocyte without immune cell involvement, by using electrical resistance across a podocyte monolayer as a surrogate marker for barrier integrity. To understand potential mechanisms underpinning this direct effect I defined the podocyte GR cistrome (using a combination of chromatin immunoprecipitation followed by massively parallel DNA sequencing and transcriptomic analysis) as well as total cell proteomics. Subsequent gene ontology analysis revealed that Gc treatment had prominent effects on podocyte motility, and these findings were validated with live-cell imaging. To gain mechanistic insight, I investigated the role of the pro-migratory small GTPase regulator Rac1, and demonstrated that treatment with Gc reduced Rac1 activity. Furthermore, the Rac1 inhibitor EHT 1864 had a direct, protective effect on the podocyte. To create a model to study the role of podocyte GR in vivo I generated a mouse line with a podocyte-specific GR deletion. IMPACT: Gc exposure produces potentially clinically-relevant effects directly on the podocyte, and Gc-induced podocyte hypomobility may underlie the clinical efficacy of these agents. Future animal studies investigating the consequences of GR deletion in the podocyte and the anti-proteinuric effects of Rac1 inhibition are warranted.

CD containing 4 videos displaying manual tracking of podocytes; raw data of 1130 glucocorticoid binding sites identified in podocytes by ChIP-Seq; raw data for glucocorticoid-regulated genes in podocytes identified by microarray.

Advisors/Committee Members: RAY, DAVID DW, WEBB, NICHOLAS NJ, Lennon, Rachel, Ray, David, Webb, Nicholas.

Subjects/Keywords: Podocyte; Glucocorticoid; Nephrotic Syndrome; Rac1

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APA (6^th Edition):

Mccaffrey, J. (2016). Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:294549

Chicago Manual of Style (16^th Edition):

Mccaffrey, James. “Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome.” 2016. Doctoral Dissertation, University of Manchester. Accessed February 27, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:294549.

MLA Handbook (7^th Edition):

Mccaffrey, James. “Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome.” 2016. Web. 27 Feb 2021.

Vancouver:

Mccaffrey J. Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Feb 27]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:294549.

Council of Science Editors:

Mccaffrey J. Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:294549

6. Abdallah, Maya. Développer des hydrogels et étudier les effets des propriétés mécaniques sur les activités biologiques des podocytes : Development of hydrogels and study the effect of their mechanical properties on podocyte behaviors.

Degree: Docteur es, Chimie et physico-chimie des matériaux, 2019, Montpellier

URL: http://www.theses.fr/2019MONTS065

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La matrice extracellulaire (MEC) contrôle et maintient les principales activités biologiques telles que la survie, la prolifération et la différenciation cellulaire. Récemment, les hydrogels ont… (more)

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La matrice extracellulaire (MEC) contrôle et maintient les principales activités biologiques telles que la survie, la prolifération et la différenciation cellulaire. Récemment, les hydrogels ont marqué une progression remarquable en tant que candidats dans le domaine de l'ingénierie tissulaire et de la médecine régénérative. Les hydrogels sont des réseaux polymériques hydrophiles ayant la capacité d’absorber une grande quantité d’eau et de fluide biologique. Les hydrogels présentent un support mécanique approprié pour les cellules tissulaires et fournissent des signaux chimiques et biologiques imitant la MEC native. Par conséquent, de nombreux hydrogels de nature biologique et chimique ont été développés dans le domaine de régénération tissulaire. Les propriétés mécaniques des hydrogels sont nécessaires pour induire les fonctions biologiques telles que l'adhésion, la prolifération et la différenciation cellulaire. L'objectif de la thèse était de développer des hydrogels à base de polymères et d'étudier l'effet de leurs propriétés physiques sur les activités biologiques des cellules podocytaires. Cette étude consiste de synthétiser et de développer des hydrogels à base de polyacrylamide hydrolysé (PAAm) où les propriétés physiques peuvent être adaptées et réglées sur une large gamme d’élasticité. Ces matériaux ont fourni une élasticité similaire à celle de la membrane basale glomérulaire (GBM) in vivo et ont représenté un candidat approprié pour la régulation des fonctions des cellules podocytaires. De même, la synthèse des hydrogels à la fois synthétiques et biologiques a pu imiter les propriétés biologiques et mécaniques de la MEC native. La combinaison des polymères à base de méthacrylate de gélatine et d'acrylamide (GelMA-AAm) a été synthétisée et analysée. Ces hydrogels ont montré des propriétés mécaniques ajustables imitant l'élasticité native du GBM du rein et une fixation significative des podocytes sans modification de surface par des protéines d'adhésion. Ce travail consiste à étudier la physiologie cellulaire et à développer un système microfluidique afin de suivre les fonctions rénales dans les états normales et défectés.

Extracellular matrix (ECM), non-cellular component, regulates and maintains the main biological activities of cells such as cellular survival, proliferation and differentiation. Recently, hydrogels scaffolds have shown a remarkable advancement as candidates for tissue engineering and regenerative medicine. Hydrogels are defined as hydrophilic polymer network having the ability to hold a large amount of water and biological fluid. Various natural and synthetic hydrogels have been studied and developed in many tissue regeneration purposes. They provide an appropriate mechanical support, chemical and biological cues mimicking the native extracellular matrix (ECM). These artificial matrices characteristics contribute to induce the cellular functions as adhesion, proliferation and differentiation. The thesis aim was to develop polymers based hydrogels and to study the effect of their…

Advisors/Committee Members: Balme, Sébastien (thesis director), Bassil, Maria (thesis director).

Subjects/Keywords: Podocyte; Matrice extracellulaire; Hydrogel; Podocyte; Extracellular Matrix; Hydrogel

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APA (6^th Edition):

Abdallah, M. (2019). Développer des hydrogels et étudier les effets des propriétés mécaniques sur les activités biologiques des podocytes : Development of hydrogels and study the effect of their mechanical properties on podocyte behaviors. (Doctoral Dissertation). Montpellier. Retrieved from http://www.theses.fr/2019MONTS065

Chicago Manual of Style (16^th Edition):

Abdallah, Maya. “Développer des hydrogels et étudier les effets des propriétés mécaniques sur les activités biologiques des podocytes : Development of hydrogels and study the effect of their mechanical properties on podocyte behaviors.” 2019. Doctoral Dissertation, Montpellier. Accessed February 27, 2021. http://www.theses.fr/2019MONTS065.

MLA Handbook (7^th Edition):

Abdallah, Maya. “Développer des hydrogels et étudier les effets des propriétés mécaniques sur les activités biologiques des podocytes : Development of hydrogels and study the effect of their mechanical properties on podocyte behaviors.” 2019. Web. 27 Feb 2021.

Vancouver:

Abdallah M. Développer des hydrogels et étudier les effets des propriétés mécaniques sur les activités biologiques des podocytes : Development of hydrogels and study the effect of their mechanical properties on podocyte behaviors. [Internet] [Doctoral dissertation]. Montpellier; 2019. [cited 2021 Feb 27]. Available from: http://www.theses.fr/2019MONTS065.

Council of Science Editors:

Abdallah M. Développer des hydrogels et étudier les effets des propriétés mécaniques sur les activités biologiques des podocytes : Development of hydrogels and study the effect of their mechanical properties on podocyte behaviors. [Doctoral Dissertation]. Montpellier; 2019. Available from: http://www.theses.fr/2019MONTS065

McMaster University

7. Khalili, Hadiseh. SHROOM3 IN THE KIDNEY.

Degree: MSc, 2015, McMaster University

URL: http://hdl.handle.net/11375/17413

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Chronic kidney disease (CKD), defined as an irreversible reduction in glomerular filtration rate, is a large public health concern. Dissecting the genetic components of CKD… (more)

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Chronic kidney disease (CKD), defined as an irreversible reduction in glomerular filtration rate, is a large public health concern. Dissecting the genetic components of CKD is required to improve our understanding of disease pathogenesis. Researchers have identified that SHROOM3, has very high associations with kidney disease and function. Shroom3 encodes an actin-binding protein important in regulating cell and tissue morphogenesis. However, there is a lack of evidence supporting a role for Shroom3 in kidney function or disease. Here, I investigated the developmental and functional role of Shroom3 in the mammalian kidney. For the first time, I described the expression pattern of Shroom3 in the embryonic and adult mouse kidneys. By performing in situ hybridization and immunohistochemistry, I demonstrated that Shroom3 is expressed in the condensing mesenchyme, podocytes, and collecting ducts. I further showed that Shroom3 protein is localized in the foot processes of podocytes, utilizing immunogold labeling and transmission electron microscopy. In order to uncover a potential role of Shroom3 in the kidney, we utilized Shroom3 knockout mice. Shroom3 mutants demonstrated marked glomerular abnormalities including cystic and degenerating glomeruli, and reduced glomerular number. Scanning and transmission electron microscopic analyses of Shroom3 mutant glomeruli revealed disruptions in podocyte morphology characterized by disorganized foot processes with less interdigitation and segmental foot processes effacement. Furthermore, immunofluorescence analysis of mutant kidneys revealed aberrant distribution of podocyte actin-associated proteins. Elucidating the underlying molecular mechanism of this abnormal podocyte architecture; v we demonstrated that in the absence of Shroom3, Rho kinase is mislocalized in the apical membrane of podocytes. As a result, mislocalized Rho kinase failed to phosphorylate non-muscle myosin and induce actomyosin contraction resulting in a patchy granular distribution of actin in the podocytes of Shroom3 mutants. Taken together, our findings established that Shroom3 is essential for proper actin organization in the podocytes through interaction with Rock. Furthermore, we took advantage of a haploinsufficiency phenotype of Shroom3 heterozygote adult mice and demonstrated these mice develop glomerulosclerosis and proteinuria. In conclusion, our studies provided evidence to support a role for Shroom3 in kidney development and disease and support the GWAS studies that suggested a correlation between SHROOM3 variants and kidney function in humans.

Thesis

Master of Science (MSc)

Advisors/Committee Members: Bridgewater, Darren, Medical Sciences.

Subjects/Keywords: Kidney; Glomerulus; Podocyte; Shroom3; CKD; Kidney Development

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APA (6^th Edition):

Khalili, H. (2015). SHROOM3 IN THE KIDNEY. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/17413

Chicago Manual of Style (16^th Edition):

Khalili, Hadiseh. “SHROOM3 IN THE KIDNEY.” 2015. Masters Thesis, McMaster University. Accessed February 27, 2021. http://hdl.handle.net/11375/17413.

MLA Handbook (7^th Edition):

Khalili, Hadiseh. “SHROOM3 IN THE KIDNEY.” 2015. Web. 27 Feb 2021.

Vancouver:

Khalili H. SHROOM3 IN THE KIDNEY. [Internet] [Masters thesis]. McMaster University; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/11375/17413.

Council of Science Editors:

Khalili H. SHROOM3 IN THE KIDNEY. [Masters Thesis]. McMaster University; 2015. Available from: http://hdl.handle.net/11375/17413

University of Guelph

8. New, Laura Alexandra. Investigation of the Role of Nephrin Phosphorylation and Associated Signaling Pathways in Kidney Podocytes.

Degree: PhD, Department of Molecular and Cellular Biology, 2014, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8008

► The integrity of the glomerulus plays a key role in prevention of kidney damage. The specialized function of the glomerular filter has led to the… (more)

▼ The integrity of the glomerulus plays a key role in prevention of kidney damage. The specialized function of the glomerular filter has led to the evolution of a unique cell type—the podocyte—whose shape and function depends on its network of actin-based ‘foot processes’. Damage to the filter—the slit diaphragm junction—formed between foot processes leads to proteinuria and can result in kidney failure. The slit diaphragm supports podocyte architecture through the IgG protein nephrin, whose cytoplasmic tail contains several conserved tyrosine residues within YDxV motifs which are phosphorylated by Fyn kinase. The significance of these tyrosines has remained elusive, but they have recently been shown to recruit the essential podocyte protein Nck. We hypothesize that phosphorylated nephrin signaling via Nck is important in the podocyte and that removal of the YDxV motifs from nephrin in vivo will result in a loss of Nck signaling and the collapse of the podocyte actin cytoskeleton. To study nephrin phosphorylation on specific tyrosines, we generated phospho-nephrin antibodies against individual YDxV motifs. These antibodies allowed us to validate that these sites are indeed phosphorylated in vivo and to demonstrate that phosphorylation on these tyrosines is altered in a podocyte injury model. This work was complemented by further study of the regulation of nephrin phosphorylation, which outlined a mechanism whereby nephrin phosphorylation is positively regulated by Nck. Recruitment of Nck to phosphorylated nephrin via its SH2 domain enables its SH3 domains to bind and activate Fyn kinase, thus increasing nephrin tyrosine phosphorylation and promoting continued engagement of nephrin signaling pathways. Finally, we investigated the importance of nephrin tyrosine phosphorylation in vivo through the nephrinY3F mouse model, which contains mutations preventing nephrin phosphorylation on the YDxV tyrosine motifs. The inability to phosphorylate these tyrosines in vivo does not prevent slit diaphragm formation, but results in podocyte foot process effacement and proteinuria with age. These results highlight the importance of phospho-nephrin signaling pathways in the podocyte, and—as altered nephrin phosphorylation is observed in human kidney disease—may contribute to a better understanding of how these pathways can be therapeutically manipulated to restore damaged podocytes. Advisors/Committee Members: Jones, Nina (advisor).

Subjects/Keywords: podocyte; nephrin; Nck; cell signaling; tyrosine phosphorylation

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APA (6^th Edition):

New, L. A. (2014). Investigation of the Role of Nephrin Phosphorylation and Associated Signaling Pathways in Kidney Podocytes. (Doctoral Dissertation). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8008

Chicago Manual of Style (16^th Edition):

New, Laura Alexandra. “Investigation of the Role of Nephrin Phosphorylation and Associated Signaling Pathways in Kidney Podocytes.” 2014. Doctoral Dissertation, University of Guelph. Accessed February 27, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8008.

MLA Handbook (7^th Edition):

New, Laura Alexandra. “Investigation of the Role of Nephrin Phosphorylation and Associated Signaling Pathways in Kidney Podocytes.” 2014. Web. 27 Feb 2021.

Vancouver:

New LA. Investigation of the Role of Nephrin Phosphorylation and Associated Signaling Pathways in Kidney Podocytes. [Internet] [Doctoral dissertation]. University of Guelph; 2014. [cited 2021 Feb 27]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8008.

Council of Science Editors:

New LA. Investigation of the Role of Nephrin Phosphorylation and Associated Signaling Pathways in Kidney Podocytes. [Doctoral Dissertation]. University of Guelph; 2014. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8008

University of Ottawa

9. Shaji, Roya. The Role of Thromboxane A2 Receptors in Diabetic Kidney Disease .

Degree: 2011, University of Ottawa

URL: http://hdl.handle.net/10393/19759

► Thromboxane receptor (TPr) activity is elevated in diabetes and contributes to complications of diabetic kidney disease (DKD). TPr blockade appears to have therapeutic potential. Several… (more)

▼ Thromboxane receptor (TPr) activity is elevated in diabetes and contributes to complications of diabetic kidney disease (DKD). TPr blockade appears to have therapeutic potential. Several rodent models of DKD show attenuation of renal damage and proteinuria upon administration of the TPr antagonist, S18886. However, the cellular targets that underlie the injurious effects of TPr activation in DKD remain to be elucidated. A pilot study in our laboratory subjected a conditionally-immortalized mouse podocyte cell line to high glucose (25 mM D-glucose) and equibiaxial mechanical stretch (an in vitro simulator of increased glomerular capillary pressure associated with glomerular hyperfiltration in early diabetes). qRT-PCR revealed that exposure of podocytes to mechanical stretch (10% elongation) and high glucose for 6 hours yielded a 9-fold increase in TPr mRNA levels vs. controls (non-stretch, 5mM D-glucose + 25mM L-glucose) (p<0.05, n=5). We hypothesized that TPr expression and activity are increased in podocytes during the onset of DKD resulting in maladaptive effects on this key glomerular filtration barrier cell type. We showed that enhanced TPr signaling threatens podocytes viablility. Cultured podocytes treated with the TPr agonist, U-46619 (1 μM) for 24 hours are more vulnerable to apoptosis as quantified by Hoescht 33342 (20% cell death p<0.001, n=3) , TUNEL (30-fold increase, ns, n=3) and Annexin-V labeling (3-fold increase, p <0.001, n=3). To further support these in vitro findings, we developed a transgenic mouse with podocyte-specific overexpression of TPr. A construct consisting of a desensitization resistant mutant of the human TPr with both N- and C-terminal HA-epitope tags under the control of an 8.3 kb fragment of the immediate 5’ mouse NPHS1 promoter was cloned, isolated and injected into FVB/n oocytes that were implanted into pseudopregnant CD1 females. Founders were characterized for TPr transgene expression, and TPr transgene mRNA levels were detected by qRT-PCR. Our in vitro results suggest that increased TPr expression in podocytes of diabetic mice may contribute to filtration barrier damage and have important implications in the development and progression of DKD.

Subjects/Keywords: podocyte; diabetic kidney disease; thromboxane A2

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APA (6^th Edition):

Shaji, R. (2011). The Role of Thromboxane A2 Receptors in Diabetic Kidney Disease . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/19759

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shaji, Roya. “The Role of Thromboxane A2 Receptors in Diabetic Kidney Disease .” 2011. Thesis, University of Ottawa. Accessed February 27, 2021. http://hdl.handle.net/10393/19759.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shaji, Roya. “The Role of Thromboxane A2 Receptors in Diabetic Kidney Disease .” 2011. Web. 27 Feb 2021.

Vancouver:

Shaji R. The Role of Thromboxane A2 Receptors in Diabetic Kidney Disease . [Internet] [Thesis]. University of Ottawa; 2011. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10393/19759.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shaji R. The Role of Thromboxane A2 Receptors in Diabetic Kidney Disease . [Thesis]. University of Ottawa; 2011. Available from: http://hdl.handle.net/10393/19759

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University

10. Chen, Junbo. Fine granular deposition of clonal immunoreactivity on podocyte cell bodies: a primary podocytopathy marker and potential clue to disease mechanism.

Degree: MS, Pathology, 2018, Boston University

URL: http://hdl.handle.net/2144/31223

► Minimal change disease (MCD) and primary (idiopathic) focal segmental glomerulosclerosis (1FSGS), referred to collectively as “primary podocytopathies”, are major causes of nephrotic syndrome in children… (more)

▼ Minimal change disease (MCD) and primary (idiopathic) focal segmental glomerulosclerosis (1FSGS), referred to collectively as “primary podocytopathies”, are major causes of nephrotic syndrome in children and adults, and are thought to be due to direct podocyte damage visible only at the electron microscopic level. Lupus podocytopathy (LP) is a newly recognized entity that involves severe podocyte injury in the setting of systemic lupus erythematosus, in the complete absence of peripheral capillary wall immune deposits. All of these pathologic diagnoses hinge on the ultrastructural finding of severe podocyte injury and foot process effacement. In addition to these ultrastructural changes, we have observed the presence of fine granular anti-IgG antibody immunoreactivity on podocyte cell bodies in kidney biopsies of patients with MCD, LP, and some patients with the tip lesion variant and NOS variants of 1FSGS. To validate this finding, we compared antibody staining from primary podocytopathy biopsies with those in biopsies from patients with other disease states, including lesions associated with severe podocyte injury in the absence of immune deposits: secondary (adaptive) focal segmental glomerulosclerosis, thin basement membrane disease, diabetic nephropathy, and renal amyloidosis. We found that a fine granular pattern of anti-IgG immunoreactivity on podocyte cell bodies is a specific morphologic feature of the primary podocytopathies, including virtually all cases of MCD that we encountered, some instances of tip lesion variant and NOS variant of 1FSGS, and one cases of LP. The antigen targeted by the anti-IgG immunostaining in these biopsies exhibited one of several oligoclonal IgG heavy chain subtype plus light chain profiles. Ultra-high resolution microscopy revealed fine linear anti-IgG staining along filtration slit diaphragms, suggesting that IgG deposition may potentially be targeting a filtration slit-associated antigen such as podocin. Our findings suggest the possibility of a direct antibody-mediated mechanism of podocyte injury in the primary podocytopathies, one that potentially targets podocyte-specific protein structures, and which may provide a specific and more rapid diagnostic marker for this group of diseases. The findings also suggest an etiologic relationship between MCD and some instances of 1FSGS. Advisors/Committee Members: Henderson, Joel M. (advisor), Andry, Christopher D. (advisor).

Subjects/Keywords: Pathology; IgG; Minimal change disease; Podocyte

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APA (6^th Edition):

Chen, J. (2018). Fine granular deposition of clonal immunoreactivity on podocyte cell bodies: a primary podocytopathy marker and potential clue to disease mechanism. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/31223

Chicago Manual of Style (16^th Edition):

Chen, Junbo. “Fine granular deposition of clonal immunoreactivity on podocyte cell bodies: a primary podocytopathy marker and potential clue to disease mechanism.” 2018. Masters Thesis, Boston University. Accessed February 27, 2021. http://hdl.handle.net/2144/31223.

MLA Handbook (7^th Edition):

Chen, Junbo. “Fine granular deposition of clonal immunoreactivity on podocyte cell bodies: a primary podocytopathy marker and potential clue to disease mechanism.” 2018. Web. 27 Feb 2021.

Vancouver:

Chen J. Fine granular deposition of clonal immunoreactivity on podocyte cell bodies: a primary podocytopathy marker and potential clue to disease mechanism. [Internet] [Masters thesis]. Boston University; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/2144/31223.

Council of Science Editors:

Chen J. Fine granular deposition of clonal immunoreactivity on podocyte cell bodies: a primary podocytopathy marker and potential clue to disease mechanism. [Masters Thesis]. Boston University; 2018. Available from: http://hdl.handle.net/2144/31223

University of Manchester

11. Mccaffrey, James. Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome.

Degree: PhD, 2016, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/podocytespecific-glucocorticoid-effects-in-childhood-nephrotic-syndrome(559e1d71-6e81-46e5-84ae-7c836e4de042).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680009

► Background: Nephrotic syndrome (NS) occurs when the glomerular filtration barrier becomes abnormally permeable, leading to the clinical triad of proteinuria, massive oedema, and hypoalbuminaemia. Historically,… (more)

▼ Background: Nephrotic syndrome (NS) occurs when the glomerular filtration barrier becomes abnormally permeable, leading to the clinical triad of proteinuria, massive oedema, and hypoalbuminaemia. Historically, NS has been thought to result from dysregulation of the immune system, although recent evidence suggests the glomerular podocyte plays a central role in disease pathogenesis. Children with NS are generally treated with an empiric course of glucocorticoid (Gc) therapy; a class of steroids which are activating ligands for the glucocorticoid receptor (GR) transcription factor. A major factor limiting the clinical utility of these agents is the marked variation observed in response to treatment. Although Gc-therapy has been the cornerstone of NS management for several decades, the mechanism of action, and target cell, remain poorly understood. Hypothesis and aims: The central hypothesis for this thesis states that glucocorticoids act directly on the podocyte to produce clinically useful effects without involvement of the immune system. Findings: Using a wild-type human podocyte cell line, I demonstrated that the basic GR-signalling mechanism is intact in the podocyte, and that glucocorticoids produce a direct, protective effect on the podocyte without immune cell involvement, by using electrical resistance across a podocyte monolayer as a surrogate marker for barrier integrity. To understand potential mechanisms underpinning this direct effect I defined the podocyte GR cistrome (using a combination of chromatin immunoprecipitation followed by massively parallel DNA sequencing and transcriptomic analysis) as well as total cell proteomics. Subsequent gene ontology analysis revealed that Gc treatment had prominent effects on podocyte motility, and these findings were validated with live-cell imaging. To gain mechanistic insight, I investigated the role of the pro-migratory small GTPase regulator Rac1, and demonstrated that treatment with Gc reduced Rac1 activity. Furthermore, the Rac1 inhibitor EHT 1864 had a direct, protective effect on the podocyte. To create a model to study the role of podocyte GR in vivo I generated a mouse line with a podocyte-specific GR deletion. Impact: Gc exposure produces potentially clinically-relevant effects directly on the podocyte, and Gc-induced podocyte hypomobility may underlie the clinical efficacy of these agents. Future animal studies investigating the consequences of GR deletion in the podocyte and the anti-proteinuric effects of Rac1 inhibition are warranted.

Subjects/Keywords: 618.92; Podocyte; Glucocorticoid; Nephrotic Syndrome; Rac1

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APA (6^th Edition):

Mccaffrey, J. (2016). Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/podocytespecific-glucocorticoid-effects-in-childhood-nephrotic-syndrome(559e1d71-6e81-46e5-84ae-7c836e4de042).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680009

Chicago Manual of Style (16^th Edition):

Mccaffrey, James. “Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome.” 2016. Doctoral Dissertation, University of Manchester. Accessed February 27, 2021. https://www.research.manchester.ac.uk/portal/en/theses/podocytespecific-glucocorticoid-effects-in-childhood-nephrotic-syndrome(559e1d71-6e81-46e5-84ae-7c836e4de042).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680009.

MLA Handbook (7^th Edition):

Mccaffrey, James. “Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome.” 2016. Web. 27 Feb 2021.

Vancouver:

Mccaffrey J. Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Feb 27]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/podocytespecific-glucocorticoid-effects-in-childhood-nephrotic-syndrome(559e1d71-6e81-46e5-84ae-7c836e4de042).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680009.

Council of Science Editors:

Mccaffrey J. Podocyte-specific glucocorticoid effects in childhood nephrotic syndrome. [Doctoral Dissertation]. University of Manchester; 2016. Available from: https://www.research.manchester.ac.uk/portal/en/theses/podocytespecific-glucocorticoid-effects-in-childhood-nephrotic-syndrome(559e1d71-6e81-46e5-84ae-7c836e4de042).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680009

University of Edinburgh

12. Miller-Hodges, Eve Victoria. WT1 in the adult kidney : podocyte maintenance and the epithelial-mesenchymal balance.

Degree: PhD, 2014, University of Edinburgh

URL: http://hdl.handle.net/1842/10039

► Glomerular diseases are the leading cause of end stage kidney disease worldwide. Podocyte injury plays a key role in the initiation and development of such… (more)

▼ Glomerular diseases are the leading cause of end stage kidney disease worldwide. Podocyte injury plays a key role in the initiation and development of such diseases, which follow a progressive course due to the limited capacity of podocytes to regenerate. Podocytes are highly specialised, terminally differentiated cells, which play a vital role in the glomerular filtration barrier. They are also the main sites of expression of the Wilms Tumour Suppressor gene, WT1, in the adult. WT1 is a complex gene, which plays an essential role in renal development by controlling the process of mesenchymal to epithelial transition that forms the nephron. Adult podocytes maintain both epithelial and mesenchymal features and continue to express high levels of WT1. Little is known about the role of WT1 in adult podocytes as previous studies have been limited due to the confounding developmental effects and embryonic lethality of existing animal models. This thesis sought to investigate the hypothesis that WT1 is an essential gene in adult kidney and plays a fundamental role in the adult podocyte. Given its role in nephron development, WT1 loss was hypothesised to result in dedifferentiation and an alteration of the epithelial-mesenchymal balance in the podocyte, affecting its specialised function. Using an inducible, conditional animal model of Wt1 loss, Wt1 was deleted from the adult, confirming its essential role in adult kidney. Wt1 deletion resulted in severe podocyte injury and failure of the glomerular filtration barrier, as well as loss of expression of key podocyte genes. Preliminary analysis suggests this was not simply due to podocyte apoptosis and/or detachment, supporting a role for Wt1 in podocyte differentiation. This was corroborated by in vitro studies that demonstrated a requirement for Wt1 for podocyte differentiation. Significantly, Wt1 loss resulted in a marked change in the expression of epithelial and mesenchymal markers in podocytes, with upregulation of mesenchymal characteristics, in keeping with a transitional stage consistent with an earlier developmental form. To investigate the mechanism behind these findings a conditionally immortalised podocyte cell line was generated as a model of Wt1 loss in vitro. In order to confirm and specifically analyse the podocyte phenotype, BAC recombineering was utilised to produce a promoter-reporter transgene construct to attempt to generate a fluorescent-labelled, podocyte specific animal model of Wt1 loss. The findings of this thesis establish that Wt1 is essential for adult podocyte function, and appears to be a key upstream regulator of podocyte differentiation. Extension of this work may allow the identification of potential targets to promote podocyte differentiation and/or regeneration in the setting of acquired and progressive glomerular disease.

Subjects/Keywords: 616.6; kidney; podocyte; epithelial-mesenchymal balance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Miller-Hodges, E. V. (2014). WT1 in the adult kidney : podocyte maintenance and the epithelial-mesenchymal balance. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/10039

Chicago Manual of Style (16^th Edition):

Miller-Hodges, Eve Victoria. “WT1 in the adult kidney : podocyte maintenance and the epithelial-mesenchymal balance.” 2014. Doctoral Dissertation, University of Edinburgh. Accessed February 27, 2021. http://hdl.handle.net/1842/10039.

MLA Handbook (7^th Edition):

Miller-Hodges, Eve Victoria. “WT1 in the adult kidney : podocyte maintenance and the epithelial-mesenchymal balance.” 2014. Web. 27 Feb 2021.

Vancouver:

Miller-Hodges EV. WT1 in the adult kidney : podocyte maintenance and the epithelial-mesenchymal balance. [Internet] [Doctoral dissertation]. University of Edinburgh; 2014. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1842/10039.

Council of Science Editors:

Miller-Hodges EV. WT1 in the adult kidney : podocyte maintenance and the epithelial-mesenchymal balance. [Doctoral Dissertation]. University of Edinburgh; 2014. Available from: http://hdl.handle.net/1842/10039

University of Edinburgh

13. Zhou, Yu Simona. Podocyte repair and recovery in kidney disease.

Degree: PhD, 2011, University of Edinburgh

URL: http://hdl.handle.net/1842/5959

► Introduction Podocytes are terminally differentiated, highly specialized glomerular cells that form the final barrier to protein loss. Podocyte injury is characterised by proteinuria. Proteinuria is… (more)

▼ Introduction Podocytes are terminally differentiated, highly specialized glomerular cells that form the final barrier to protein loss. Podocyte injury is characterised by proteinuria. Proteinuria is an important prognostic marker in kidney diseases, and lowering proteinuria has become a principal clinical goal. Compelling evidence supports the notion that continuing loss of podocytes plays a major role in the initiation and progression of glomerular diseases. It is my hypothesis that interventions that reduce the disruption by rescuing susceptible podocytes next to injured ones are potential therapies to restore podocyte phenotype and filtration behaviour, thereby protecting the kidney from progressive deterioration. Prevention of this damage, or ways to aid its recovery, could therefore be important to improving the management of human kidney diseases. Methods Transgenic mice expressing the human diphtheria toxin receptor on podocytes had been previously generated in our laboratory. Characterization of two lines showed that graded specific podocyte injury could be induced by single intraperitoneal injection of diphtheria toxin. Eight-week intervention studies involved administration of oral drug in water or food from 24h after toxin injection. Two control groups received no drug or were non-transgenic (wild-type) littermates. Primary endpoints were glomerulosclerosis and kidney function (serum creatinine). Other readouts included blood pressure, albuminuria, serum albumin, podocyte quantification and collagen staining of kidney. The angiotensin converting enzyme inhibitor (ACEi) captopril was tested because of its proven protective effect on renal function in patients with proteinuria. Subsequently another proteinuria-reducing drug, the endothelin receptor A antagonist sitaxsentan was tested alone and in combination with captopril. Results Captopril reduced proteinuria and ameliorated scarring, with matrix accumulation and glomerulosclerosis falling almost to baseline. Podocyte counts were reduced after toxin administration and showed no significant recovery irrespective of captopril treatment. In the following sitaxsentan and captopril combined intervention study, glomerular scarring was significantly reduced in all drug-treated groups either alone or in combination, but only combination drug treatment reduced glomerular damage to levels comparable to wild-type controls, demonstrating a synergistic effect of the two agents. Similarly, serum creatinine was lowered further in combined but not single drug-treated groups. Blood pressure of all drug treated mice was lowered compared to the placebo group. Surprisingly in this second study there were no significant differences in proteinuria between treated and untreated groups. Conclusion These results support the hypothesis that continuing podocyte dysfunction is a key abnormality in proteinuric disease, and plays a major role in progressive glomerulosclerosis. Both captopril and sitaxsentan alone or in combination provided protection without substantial preservation or…

Subjects/Keywords: 616.6; Podocyte; kidney disease; glomerulosclerosis; FSGS

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhou, Y. S. (2011). Podocyte repair and recovery in kidney disease. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/5959

Chicago Manual of Style (16^th Edition):

Zhou, Yu Simona. “Podocyte repair and recovery in kidney disease.” 2011. Doctoral Dissertation, University of Edinburgh. Accessed February 27, 2021. http://hdl.handle.net/1842/5959.

MLA Handbook (7^th Edition):

Zhou, Yu Simona. “Podocyte repair and recovery in kidney disease.” 2011. Web. 27 Feb 2021.

Vancouver:

Zhou YS. Podocyte repair and recovery in kidney disease. [Internet] [Doctoral dissertation]. University of Edinburgh; 2011. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1842/5959.

Council of Science Editors:

Zhou YS. Podocyte repair and recovery in kidney disease. [Doctoral Dissertation]. University of Edinburgh; 2011. Available from: http://hdl.handle.net/1842/5959

14. N'Gome Sendeyo, Kelhia. Immunopathologie des podocytopathies acquises : rôle de c-mip dans les perturbations immunitaires et podocytaires : Immunopathology of acquired podocytopathy : role of c-mip in alterations of immune system and podocytes.

Degree: Docteur es, Physiopathologie, 2013, Université Paris-Est

URL: http://www.theses.fr/2013PEST0116

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Le Syndrome Néphrotique à Lésions Glomérulaires Minimes (SNLGM) et la glomérulonéphrite extra membraneuse (GEM) sont deux podocytopathies primitives d'origine immunitaire associant des altérations immunes et… (more)

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Le Syndrome Néphrotique à Lésions Glomérulaires Minimes (SNLGM) et la glomérulonéphrite extra membraneuse (GEM) sont deux podocytopathies primitives d'origine immunitaire associant des altérations immunes et des atteintes podocytaires à l'origine d'un syndrome néphrotique. Cependant, bien que l'origine dysimmunitaire soit confortée par de nombreux arguments cliniques, les mécanismes impliqués restent obscurs. Initialement identifié dans les lymphocytes T (LT) de patients en phase de poussée de SNLGM, le gène c-mip est également exprimé dans les podocytes de patients atteints de SNLGM et de GEM, alors qu'il est physiologiquement réprimé. Ainsi, les objectifs de ce travail étaient : 1) appréhender le rôle de c-mip dans le LT d'une part à travers l'étude d'un modèle murin transgénique (Tg), et 2) comprendre la fonction de c-mip au niveau du podocyte grâce au modèle expérimental de GEM humaine induit chez le rat.Le modèle murin Tg Lck-cmip surexprime spécifiquement c-mip dans les LT matures périphériques. Cette surexpression est à l'origine d'un phénotype lymphocytaire altéré marqué par une accumulation de LT naïf, et une inhibition de la synthèse de cytokines de type TH1 et TH2, après une activation T spécifique ex vivo. Cette régulation négative est associée à une accumulation des formes inactives des kinases de la famille des Src et un blocage du recrutement des lipids rafts nécessaire à la formation de la synapse immunologique. Ces résultats suggèrent donc que c-mip est un régulateur négatif de l'activation T impliqué dans la signalisation proximale lymphocytaire et pourrait être impliqué dans l'hyporéactivité lymphocytaire observée chez les patients atteints de SNLGM actif.L'étude de la néphrite de Heymann passive, un modèle expérimental de GEM humaine, montre que l'induction podocytaire de c-mip coïncide avec l'apparition de la protéinurie. Cette surexpression est associée d'une part, à une diminution des taux de synaptopodine qui engendre une diminution de l'activité RhoA, à l'origine d'une désorganisation du cytosquelette podocytaire, et d'autre part à une induction de DAPK (death-associated protein kinase) et ILK (Integrin Linked Kinase) impliquées dans des phénomènes pro-apoptotiques. La cyclosporine A en inhibant l'expression de c-mip restaure les taux de DAPK et ILK ainsi que l'activité RhoA. Ainsi dans le podocyte, c-mip semble impliquer dans les troubles de la signalisation podocytaire aboutissant à une protéinurie néphrotique.C-mip semble donc jouer un rôle crucial dans les perturbations podocytaires et lymphocytaires observées chez les patients atteints de podocytopathies primitives et représente à ce titre une cible thérapeutique.Mots clefs :C-mip, Syndrome Néphrotique à Lésions Glomérulaires Minimes, Glomerulonéphrite Extra Membraneuse, signalisation proximale, lymphocyte T, podocyte, cytosquelette

Minimal Change Nephrotic Syndrome (MCNS) and Membranous Nephropathy (MN) are two primitive immune podocytopathies associating immune alterations and podocyte damage ultimately leading to proteinuria.…

Advisors/Committee Members: Sahali, Dil (thesis director).

Subjects/Keywords: Lymphocytes T; C-Mip; Snlgm; Podocyte; Gem; T lymphocyte; C-Mip; Mcns; Podocyte; Mn; 616.079

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APA (6^th Edition):

N'Gome Sendeyo, K. (2013). Immunopathologie des podocytopathies acquises : rôle de c-mip dans les perturbations immunitaires et podocytaires : Immunopathology of acquired podocytopathy : role of c-mip in alterations of immune system and podocytes. (Doctoral Dissertation). Université Paris-Est. Retrieved from http://www.theses.fr/2013PEST0116

Chicago Manual of Style (16^th Edition):

N'Gome Sendeyo, Kelhia. “Immunopathologie des podocytopathies acquises : rôle de c-mip dans les perturbations immunitaires et podocytaires : Immunopathology of acquired podocytopathy : role of c-mip in alterations of immune system and podocytes.” 2013. Doctoral Dissertation, Université Paris-Est. Accessed February 27, 2021. http://www.theses.fr/2013PEST0116.

MLA Handbook (7^th Edition):

N'Gome Sendeyo, Kelhia. “Immunopathologie des podocytopathies acquises : rôle de c-mip dans les perturbations immunitaires et podocytaires : Immunopathology of acquired podocytopathy : role of c-mip in alterations of immune system and podocytes.” 2013. Web. 27 Feb 2021.

Vancouver:

N'Gome Sendeyo K. Immunopathologie des podocytopathies acquises : rôle de c-mip dans les perturbations immunitaires et podocytaires : Immunopathology of acquired podocytopathy : role of c-mip in alterations of immune system and podocytes. [Internet] [Doctoral dissertation]. Université Paris-Est; 2013. [cited 2021 Feb 27]. Available from: http://www.theses.fr/2013PEST0116.

Council of Science Editors:

N'Gome Sendeyo K. Immunopathologie des podocytopathies acquises : rôle de c-mip dans les perturbations immunitaires et podocytaires : Immunopathology of acquired podocytopathy : role of c-mip in alterations of immune system and podocytes. [Doctoral Dissertation]. Université Paris-Est; 2013. Available from: http://www.theses.fr/2013PEST0116

Universidade do Rio Grande do Sul

15. Rodrigues, Patrícia Garcia. Expressão gênica de moléculas associadas ao podócito em pacientes portadores de glomerulopatias proteinúricas.

Degree: 2012, Universidade do Rio Grande do Sul

URL: http://hdl.handle.net/10183/56680

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Introdução: A injúria ao podócito glomerular tem um papel crítico para o surgimento de proteinúria em diferentes glomerulopatias. Neste estudo avaliamos a expressão gênica das… (more)

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Introdução: A injúria ao podócito glomerular tem um papel crítico para o surgimento de proteinúria em diferentes glomerulopatias. Neste estudo avaliamos a expressão gênica das proteínas associadas ao podócito em biópsias renais e na urina simultaneamente em pacientes com glomerulopatias proliferativas (GPP) e não proliferativas (GPNP) proteinúricas, assim como a efeito do tratamento imunossupressor sobre a expressão destas moléculas. Material e Métodos: Setenta e cinco pacientes adultos foram incluídos, 35 com diagnóstico de GPNP e 41 casos de GPP. Vinte e um indivíduos sem doença renal foram incluídos como controles. O RNAm foi quantificado no tecido renal (basal) e em células do sedimento urinário (na biópsia, aos 6 e 12 meses) dos genes nefrina, podocina, podocalixina, sinaptopodina e alfa actinina-4 por PCR em tempo real. A expressão gênica foi correlacionada com a proteinúria e a função renal, e a variação do RNAm ao longo do tempo foi comparada entre os grupos pela Equação de Estimativas Generalizadas. Resultados: O RNAm dos genes (exceto da sinaptopodina) no tecido estava significativamente reduzido no grupo GPNP. No grupo GPP, a expressão também foi menor, mas apenas o gene da podocina teve diferença estatística comparado aos controles. Em paralelo, o RNAm dos mesmos genes na urina basal foi mais elevado nos pacientes, e mais marcadamente no grupo GPP. Após seis meses de tratamento imunossupressor associado ou não a inibidores da angiotensina, no grupo GPP houve uma redução significativa da expressão de podocina, podocalixina e alfa actinina-4 aos 6 e 12 meses quando comparando ao nível basal (p<0,001). No grupo GPNP, apenas a alfa actinina-4 diminuiu (p=0,008) com uma tendência de redução da podocalixina (p=0,08). Verificou-se uma forte correlação entre os genes na biópsia (exceto com sinaptopodina), mas na urina esta correlação foi fraca. Houve correlação moderada mas significativa dos genes na urina com a proteinúria basal e dos 6 meses, mas nenhum gene correlacionou-se com a taxa de filtração glomerular. Conclusão: Nestes pacientes com glomerulopatias proteinúricas em fase aguda de doença, a expressão gênica de proteínas associadas ao podócito estava reduzida na biópsia renal concomitante com aumento da excreção urinária, sugerindo a presença de podocitopenia intra-renal e podocitúria, respectivamente. O RNAm destes genes reduziu em paralelo com a proteinúria com o uso de imunossupressores, sugerindo reorganização estrutural dos podócitos. Os resultados deste estudo não são conclusivos sobre diferenças qualitativas da podocitopatia com base em tipos histológicos específicos.

Introduction: Injury to the glomerular podocyte has a critical role in the development of proteinuria in different glomerulopathies. In this study, gene expression of podocyte-associated proteins was evaluated in kidney biopsies and urine simultaneously in patients with proliferative (PGP) and non proliferative (NPGP) glomerulopathies. The effect of immunosuppressive treatment on the expression of these molecules was also studied.…

Advisors/Committee Members: Veronese, Francisco José Veríssimo.

Subjects/Keywords: Podocyte; Glomerulonefrite; Glomerulopathies; Podócitos; Expressão gênica; Gene expression; Podocin; Nephrin

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APA (6^th Edition):

Rodrigues, P. G. (2012). Expressão gênica de moléculas associadas ao podócito em pacientes portadores de glomerulopatias proteinúricas. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/56680

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rodrigues, Patrícia Garcia. “Expressão gênica de moléculas associadas ao podócito em pacientes portadores de glomerulopatias proteinúricas.” 2012. Thesis, Universidade do Rio Grande do Sul. Accessed February 27, 2021. http://hdl.handle.net/10183/56680.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rodrigues, Patrícia Garcia. “Expressão gênica de moléculas associadas ao podócito em pacientes portadores de glomerulopatias proteinúricas.” 2012. Web. 27 Feb 2021.

Vancouver:

Rodrigues PG. Expressão gênica de moléculas associadas ao podócito em pacientes portadores de glomerulopatias proteinúricas. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2012. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10183/56680.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rodrigues PG. Expressão gênica de moléculas associadas ao podócito em pacientes portadores de glomerulopatias proteinúricas. [Thesis]. Universidade do Rio Grande do Sul; 2012. Available from: http://hdl.handle.net/10183/56680

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Guelph

16. Stringer, Colin D.M. Development of an inducible and reversible mouse model of podocyte effacement.

Degree: MS, Department of Molecular and Cellular Biology, 2011, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/2935

► Podocytes are specialized epithelial cells which wrap glomerular capillaries with numerous interdigitating foot processes (FP). Between adjacent FPs a unique junction, the slit diaphragm (SD),… (more)

Subjects/Keywords: nephropathy; proteinuria; glomerular filtration; podocyte; slit diaphragm; Nck; transgenic mouse model

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APA (6^th Edition):

Stringer, C. D. M. (2011). Development of an inducible and reversible mouse model of podocyte effacement. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/2935

Chicago Manual of Style (16^th Edition):

Stringer, Colin D M. “Development of an inducible and reversible mouse model of podocyte effacement.” 2011. Masters Thesis, University of Guelph. Accessed February 27, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/2935.

MLA Handbook (7^th Edition):

Stringer, Colin D M. “Development of an inducible and reversible mouse model of podocyte effacement.” 2011. Web. 27 Feb 2021.

Vancouver:

Stringer CDM. Development of an inducible and reversible mouse model of podocyte effacement. [Internet] [Masters thesis]. University of Guelph; 2011. [cited 2021 Feb 27]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/2935.

Council of Science Editors:

Stringer CDM. Development of an inducible and reversible mouse model of podocyte effacement. [Masters Thesis]. University of Guelph; 2011. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/2935

17. Martin, Claire. Characterization of signaling pathways regulating nephrin endocytosis in kidney podocytes: novel roles for Nck and ShcA adaptor proteins.

Degree: PhD, Department of Molecular and Cellular Biology, 2017, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/12112

► Kidney podocytes maintain blood filtration selectivity through a network of actin-based projections termed foot processes. The slit diaphragm is a molecular barrier that lies laterally… (more)

▼ Kidney podocytes maintain blood filtration selectivity through a network of actin-based projections termed foot processes. The slit diaphragm is a molecular barrier that lies laterally between foot processes and acts as a discerning filtration pore. Nephrin is a key component of this barrier and disrupted nephrin trafficking is suggested to be a source of filtration breakdown, although evidence of this within the complexity of the body remains incomplete. Further, although nephrin’s tyrosine phosphorylation is implicated in its trafficking, the binding partner(s) that facilitate these phospho-dependent mechanisms remain unidentified. Using several acute injury mouse models, we first demonstrate that nephrin tyrosine phosphorylation is commonly disrupted in the injured podocyte and that this disturbs connections between nephrin and Nck, a cytoskeletal adaptor. Targeted genetic disruption of nephrin/Nck interactions further exacerbates disease in mice, verifying a crucial role for nephrin/Nck signaling in withstanding insult. We next characterized a fundamental role for Nck in mediating recruitment of actin and the endocytic scission engine dynamin in late stages of nephrin endocytosis, which required nephrin’s tyrosine phosphorylation. Disruption of nephrin/Nck binding in podocytes in vivo and in cell models led to accumulation of nephrin in endocytic pits on the cell surface and this accompanied progressive barrier demise in mice. Interestingly, aberrant activation of this mechanism could also initiate disease, highlighting a requirement for tight regulation of this apparatus for barrier maintenance. Our final investigations revealed ShcA as a novel nephrin phosphotyrosine binding partner and modulator of nephrin trafficking. ShcA is normally expressed in low levels within podocytes and we identified a stark upregulation of ShcA in a rat model of kidney disease, concurrent with internalization of nephrin and barrier breakdown. In cell–based studies, we demonstrated that ShcA overexpression promotes phospho-mediated nephrin internalization. Upregulated ShcA gene and protein expression were also observed in several human kidney diseases, supporting the clinical relevance of this signaling pathway. Collectively, this work has identified Nck and ShcA as two novel mediators of phospho-dependent nephrin endocytosis. Integration of these pathways into the larger framework of nephrin trafficking reamins an important objective for future work. Advisors/Committee Members: Jones, Nina (advisor).

Subjects/Keywords: kidney; podocyte; nephrin

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10 more images…

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APA (6^th Edition):

Martin, C. (2017). Characterization of signaling pathways regulating nephrin endocytosis in kidney podocytes: novel roles for Nck and ShcA adaptor proteins. (Doctoral Dissertation). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/12112

Chicago Manual of Style (16^th Edition):

Martin, Claire. “Characterization of signaling pathways regulating nephrin endocytosis in kidney podocytes: novel roles for Nck and ShcA adaptor proteins.” 2017. Doctoral Dissertation, University of Guelph. Accessed February 27, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/12112.

MLA Handbook (7^th Edition):

Martin, Claire. “Characterization of signaling pathways regulating nephrin endocytosis in kidney podocytes: novel roles for Nck and ShcA adaptor proteins.” 2017. Web. 27 Feb 2021.

Vancouver:

Martin C. Characterization of signaling pathways regulating nephrin endocytosis in kidney podocytes: novel roles for Nck and ShcA adaptor proteins. [Internet] [Doctoral dissertation]. University of Guelph; 2017. [cited 2021 Feb 27]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/12112.

Council of Science Editors:

Martin C. Characterization of signaling pathways regulating nephrin endocytosis in kidney podocytes: novel roles for Nck and ShcA adaptor proteins. [Doctoral Dissertation]. University of Guelph; 2017. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/12112

University of Miami

18. Sloan, Alexis Joanna. The Role of Nuclear Factor of Activated T-Cells in Chronic Kidney Disease.

Degree: PhD, Cell Biology and Anatomy (Medicine), 2015, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/1443

► Aberrant elevation in cytoplasmic calcium levels in podocytes cause changes in podocyte morphology and glomerular permeability. The phosphatase calcineurin responds to elevated calcium by… (more)

Subjects/Keywords: NFAT; FSGS; Minimal Change Disease; Chronic Kidney Disease; podocyte

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APA (6^th Edition):

Sloan, A. J. (2015). The Role of Nuclear Factor of Activated T-Cells in Chronic Kidney Disease. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/1443

Chicago Manual of Style (16^th Edition):

Sloan, Alexis Joanna. “The Role of Nuclear Factor of Activated T-Cells in Chronic Kidney Disease.” 2015. Doctoral Dissertation, University of Miami. Accessed February 27, 2021. https://scholarlyrepository.miami.edu/oa_dissertations/1443.

MLA Handbook (7^th Edition):

Sloan, Alexis Joanna. “The Role of Nuclear Factor of Activated T-Cells in Chronic Kidney Disease.” 2015. Web. 27 Feb 2021.

Vancouver:

Sloan AJ. The Role of Nuclear Factor of Activated T-Cells in Chronic Kidney Disease. [Internet] [Doctoral dissertation]. University of Miami; 2015. [cited 2021 Feb 27]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1443.

Council of Science Editors:

Sloan AJ. The Role of Nuclear Factor of Activated T-Cells in Chronic Kidney Disease. [Doctoral Dissertation]. University of Miami; 2015. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1443

Boston University

19. Belghasem, Mostafa. Pathological and molecular profiling in hypertension-induced glomerular injury.

Degree: PhD, Pathology & Laboratory Medicine, 2015, Boston University

URL: http://hdl.handle.net/2144/13940

► The increased prevalence of chronic kidney disease (CKD) has become a major global health burden. This increase in CKD burden parallels the increase in hypertension… (more)

Subjects/Keywords: Pathology; Chronic kidney disease; Glomerulosclerosis; Hypertension; Podocyte; Mouse models

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APA (6^th Edition):

Belghasem, M. (2015). Pathological and molecular profiling in hypertension-induced glomerular injury. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/13940

Chicago Manual of Style (16^th Edition):

Belghasem, Mostafa. “Pathological and molecular profiling in hypertension-induced glomerular injury.” 2015. Doctoral Dissertation, Boston University. Accessed February 27, 2021. http://hdl.handle.net/2144/13940.

MLA Handbook (7^th Edition):

Belghasem, Mostafa. “Pathological and molecular profiling in hypertension-induced glomerular injury.” 2015. Web. 27 Feb 2021.

Vancouver:

Belghasem M. Pathological and molecular profiling in hypertension-induced glomerular injury. [Internet] [Doctoral dissertation]. Boston University; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/2144/13940.

Council of Science Editors:

Belghasem M. Pathological and molecular profiling in hypertension-induced glomerular injury. [Doctoral Dissertation]. Boston University; 2015. Available from: http://hdl.handle.net/2144/13940

Boston University

20. Milo Rasouly, Hila. Discovery and analysis of genes important in kidney development and disease.

Degree: PhD, Genetics & Genomics, 2015, Boston University

URL: http://hdl.handle.net/2144/13984

► Abnormal kidney development is a relatively prevalent health issue; however, the genetic basis is mostly unknown. The aim of this thesis is to identify genes… (more)

▼ Abnormal kidney development is a relatively prevalent health issue; however, the genetic basis is mostly unknown. The aim of this thesis is to identify genes important in kidney development and disease and to study their molecular functions. We hypothesized that human diseases associated with kidney anomalies can uncover novel genes important in kidney development and disease. The thesis is divided into three independent projects that examined three genes (i.e. Zeb2, Ilk, Robo2) at three stages of mouse kidney development: nephrogenesis, glomerular podocyte, and early ureteric bud outgrowth. In the first project, we identified Zeb2, a gene encoding the zinc finger E-box binding homeobox 2 transcription factor that is mutated in the Mowat Wilson syndrome, as a novel gene important in nephrogenesis. Zeb2 conditional knockout mice (Zeb2 cKO) develop glomerulocystic kidney disease with many atubular glomeruli and decreased expression of proximal tubular markers before cyst formation. These data suggest that abnormal nephrogenesis leads to the congenital atubular glomeruli and primary glomerular cysts in the Zeb2 cKO mice. This study implies that ZEB2 is a novel candidate gene for glomerular cystic disease in patients. Additionally we found that Pkd1, the gene mutated in autosomal dominant polycystic kidney disease, is upregulated in non-cystic glomeruli and knockout of one copy of the Pkd1 gene exacerbates the cystic phenotype of the Zeb2 cKO mice. These findings suggest a genetic interaction between Zeb2 and Pkd1 and that Zeb2 might be a novel PKD1 modifier. In the second project, we studied the roles of integrin-linked kinase (ILK) and roundabout 2 (ROBO2) in glomerular podocytes. We found that ILK and ROBO2 form a protein complex, and that loss of Robo2 improves survival and alleviates the podocyte and basement membrane abnormalities seen in Ilk knockout mice. In the third project, using microarray gene expression analysis, we found lower gene expression levels of extracellular matrix proteins during early ureteric bud outgrowth in the Robo2 homozygous knockout embryos as compared to wild type controls. These findings suggest that ROBO2 may regulate extracellular matrix components in the kidney. In conclusion, we found a new role for Zeb2 in nephrogenesis, and identified a novel function of Robo2 in regulating extracellular matrix gene expression in podocytes and during early kidney development.

Subjects/Keywords: Developmental biology; Robo2; Zeb2; Glomerulocystic; Kidney; Podocyte; Transgenic

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APA (6^th Edition):

Milo Rasouly, H. (2015). Discovery and analysis of genes important in kidney development and disease. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/13984

Chicago Manual of Style (16^th Edition):

Milo Rasouly, Hila. “Discovery and analysis of genes important in kidney development and disease.” 2015. Doctoral Dissertation, Boston University. Accessed February 27, 2021. http://hdl.handle.net/2144/13984.

MLA Handbook (7^th Edition):

Milo Rasouly, Hila. “Discovery and analysis of genes important in kidney development and disease.” 2015. Web. 27 Feb 2021.

Vancouver:

Milo Rasouly H. Discovery and analysis of genes important in kidney development and disease. [Internet] [Doctoral dissertation]. Boston University; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/2144/13984.

Council of Science Editors:

Milo Rasouly H. Discovery and analysis of genes important in kidney development and disease. [Doctoral Dissertation]. Boston University; 2015. Available from: http://hdl.handle.net/2144/13984

Harvard University

21. Sidhom, Eriene-Heidi. Unraveling the Molecular and Cellular Complexities of the Kidney in Health and Disease.

Degree: PhD, 2019, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029547

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Chronic kidney disease (CKD) affects over 500 million people worldwide, and despite this significant disease burden, therapeutic innovation in nephrology has lagged. This trend is… (more)

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Chronic kidney disease (CKD) affects over 500 million people worldwide, and despite this significant disease burden, therapeutic innovation in nephrology has lagged. This trend is partly attributed both to an incomplete understanding of the molecular mechanisms of kidney dysfunction and a lack of appropriate in vitro and in vivo models, a reflection of the multifactorial nature CKD and the complex cellular complexity of the kidney. Genetically defined rare diseases can provide insight into disease pathogenesis. We thus, sought to understand the mechanism underlying a rare Coenzyme Q (CoQ)-deficiency-associated podocytopathy. Podocytes are a terminally differentiated, post-mitotic cell type, essential for kidney filter function. An in vitro podocyte model of CoQ deficiency revealed a susceptibility to ROS-mediated injury and a perturbation in polyunsaturated fatty acid metabolism. Single nucleus sequencing from the kidneys of CoQ-deficient mice validated podocyte-specific transcriptomic changes consistent with in vitro findings and revealed a novel, disease-specific parietal epithelial cell population. Our analysis further revealed the BRAF-targeting GDC-0879 as a putative therapeutic strategy. Kidney organoids derived from human induced pluripotent stem cells (iPSCs) are an emerging technology with the potential to both recapitulate the cellular diversity of the kidney and to further our understanding of disease. However, this progress is dependent on understanding the reproducibility and quality of organoids derived from multiple patients-donors. Thus, we generated a 412,358 single cell census of 47 organoid and iPSC samples derived from four cell lines across four time points of differentiation. All cell lines contained representative segments of the developing nephron, but varied in their proportions of cell types and in the presence of off-target populations. Comparison to single cell fetal kidney data revealed that the organoids were most similar to first trimester fetal kidney. While long-term in vitro culture did not affect organoid composition, in vivo transplantation of organoids resulted in reduced off-target populations.

Medical Sciences

Advisors/Committee Members: Haigis, Marcia (advisor), Biddinger, Sudha (committee member), Parikh, Samir (committee member), He, John Cijiang (committee member).

Subjects/Keywords: Kidney; podocyte; organoid; Coenzyme Q; PDSS2; nephrotic syndrome; polyunsaturated fatty acids

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APA (6^th Edition):

Sidhom, E. (2019). Unraveling the Molecular and Cellular Complexities of the Kidney in Health and Disease. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029547

Chicago Manual of Style (16^th Edition):

Sidhom, Eriene-Heidi. “Unraveling the Molecular and Cellular Complexities of the Kidney in Health and Disease.” 2019. Doctoral Dissertation, Harvard University. Accessed February 27, 2021. http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029547.

MLA Handbook (7^th Edition):

Sidhom, Eriene-Heidi. “Unraveling the Molecular and Cellular Complexities of the Kidney in Health and Disease.” 2019. Web. 27 Feb 2021.

Vancouver:

Sidhom E. Unraveling the Molecular and Cellular Complexities of the Kidney in Health and Disease. [Internet] [Doctoral dissertation]. Harvard University; 2019. [cited 2021 Feb 27]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029547.

Council of Science Editors:

Sidhom E. Unraveling the Molecular and Cellular Complexities of the Kidney in Health and Disease. [Doctoral Dissertation]. Harvard University; 2019. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029547

University of Manchester

22. Hosawi, Salman. Global proteomic analysis of insulin action in glomerular podocytes.

Degree: PhD, 2018, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/global-proteomic-analysis-of-insulin-action-in-glomerular-podocytes(8783e6b4-8dc8-4ba0-92f7-6f193eb4c5af).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.771402

► Introduction & Aim: Insulin signalling contributes to diverse cellular activities including protein synthesis, proliferation and cell survival. Insulin resistance describes the inability of cells to… (more)

▼ Introduction & Aim: Insulin signalling contributes to diverse cellular activities including protein synthesis, proliferation and cell survival. Insulin resistance describes the inability of cells to activate the insulin signalling pathway effectively. This leads to pathological effects in multiple organ systems including the kidney. In diabetic nephropathy (DN), there is progressive glomerular dysfunction and recent studies have demonstrated that the podocyte is a direct target for insulin action. Furthermore, abrogation of insulin signalling specifically in podocytes leads to progressive kidney damage and eventually kidney failure. This study utilised a global unbiased proteomic approach to examine insulin signalling in podocytes under normal and resistant conditions, with the aim of identifying key molecules that could be targeted for diagnostic or therapeutic purposes. Methods: A human immortalised, thermo-sensitive podocyte cell line over-expressing the human Insulin receptor (INSR) was used under normal or resistant conditions (induced by the free fatty acid palmitate). The INSR was isolated following insulin stimulation (100nM) from whole cell immunoprecipitation (IP) or plasma membrane using in situ immunoprecipitation (In situ-IP) at different time points, and label-free mass spectrometry (MS) was used to detect proteins interactions with the INSR in at the receptor level. Western blotting and immunofluorescene imaging (IF) were used for candidate validation and glucose uptake and the electrical cell-substrate impedance sensing assay (ECIS) was employed to assess functional responses to insulin stimulation. Results: The MS analysis of the INSR isolated from the human podocytes resulted in the detection of 26 known INSR direct binders, and the bioinformatic analysis also led to the identification of doublecortin domain-containing protein 2 (DCDC2) and the microtubule crosslinking factor 1 (MTCL1) as novel INSR binding proteins. The interaction of DCDC2 and MTCL1 with the INSR was confirmed by IP and IF, and under insulin resistance conditions DCDC2 displayed increased association with the INSR, while MTCL1 showed no significant change. The knockdown of DCDC2 and MTCL1 using specific siRNA in the podocytes resulted in abnormal cellular localisation of the INSR compared to controls, and the podocytes exhibited significant morphological changes. Furthermore, the knockdown negatively affected podocyte migration and cell-cell / cell-matrix junction formation. Conclusion: This study provides insight into the complexity and specificity of insulin signalling in podocytes, and may explain how insulin resistance can affect the integrity of the glomerular filtration barrier in chronic kidney disease such as DN. The bioinformatics analysis of the INSR complex led to the discovery and confirmation of DCDC2 and MTCL1 as novel INSR binding proteins, and the validation experiments demonstrated the involvement of these targets in insulin signalling and podocyte biology.

Subjects/Keywords: Proteomics; Insulin resistance; Diabetes; Podocyte; Insulin signalling; Free fatty acids

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APA (6^th Edition):

Hosawi, S. (2018). Global proteomic analysis of insulin action in glomerular podocytes. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/global-proteomic-analysis-of-insulin-action-in-glomerular-podocytes(8783e6b4-8dc8-4ba0-92f7-6f193eb4c5af).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.771402

Chicago Manual of Style (16^th Edition):

Hosawi, Salman. “Global proteomic analysis of insulin action in glomerular podocytes.” 2018. Doctoral Dissertation, University of Manchester. Accessed February 27, 2021. https://www.research.manchester.ac.uk/portal/en/theses/global-proteomic-analysis-of-insulin-action-in-glomerular-podocytes(8783e6b4-8dc8-4ba0-92f7-6f193eb4c5af).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.771402.

MLA Handbook (7^th Edition):

Hosawi, Salman. “Global proteomic analysis of insulin action in glomerular podocytes.” 2018. Web. 27 Feb 2021.

Vancouver:

Hosawi S. Global proteomic analysis of insulin action in glomerular podocytes. [Internet] [Doctoral dissertation]. University of Manchester; 2018. [cited 2021 Feb 27]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/global-proteomic-analysis-of-insulin-action-in-glomerular-podocytes(8783e6b4-8dc8-4ba0-92f7-6f193eb4c5af).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.771402.

Council of Science Editors:

Hosawi S. Global proteomic analysis of insulin action in glomerular podocytes. [Doctoral Dissertation]. University of Manchester; 2018. Available from: https://www.research.manchester.ac.uk/portal/en/theses/global-proteomic-analysis-of-insulin-action-in-glomerular-podocytes(8783e6b4-8dc8-4ba0-92f7-6f193eb4c5af).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.771402

23. Lassén, Emelie. Molecular perspectives on glomerular cell physiology in chronic kidney disease.

Degree: 2019, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/59539

► Glomerulonephritis is one of the most common causes of chronic kidney disease (CKD) in the world. Recent establishment of guidelines for classification of CKD in… (more)

▼ Glomerulonephritis is one of the most common causes of chronic kidney disease (CKD) in the world. Recent establishment of guidelines for classification of CKD in five stages has led to increased awareness of the risks of comorbidity and mortality, also in patients with early stages of disease, and the need to further advance our understanding of their pathogenic mechanisms. Many glomerular diseases are complex and curative treatment options are currently lacking, in part due to the difficulties to identify new molecular targets for treatment. The work included in this thesis focuses on physiological and pathophysiological mechanisms in glomerular mesangial cells and podocytes, especially in the disease IgA nephropathy (IgAN). Through analysis of mesangial cells derived from IgAN patient biopsies we found that patient cells proliferated more than healthy control cells in response to pathogenic IgA or PDGF-BB. They also released more PDGF-BB and IL-6 into the growth medium than control cells in response to the same stimuli, suggesting an increased sensitivity and thereby susceptibility for disease in the patient cells. A subsequent study of the glomerular transcriptome from patients with IgAN and healthy kidney donors was done by microarray and bioinformatics analysis. It demonstrated that differential expression of mesangial cell specific standard genes was prominent in IgAN, while podocyte standard genes were less significant in this context. The mesangial cell standard genes also correlated to patients’ clinical parameters after z-score transformation. Finally, we identified potential functions for the protein CKAP4 in glomerular cells, where it appears to be involved in regulation of proliferative signaling in mesangial cells through association with the PDGF pathway, and in maintenance of the podocyte structural stability through effects on the actin cytoskeleton. In conclusion, our findings support previous knowledge about the central role of mesangial cells in IgAN, as well as suggest that these cells can have an altered susceptibility to disease. We also identified glomerular transcriptomic and mesangial cell proteomic pathways relevant for further research into development and progression of IgAN. We also found that CKAP4 is involved in disease mechanisms of mesangial cells and podocytes, warranting further investigation into the functions of the protein in health as well as in different forms of glomerular disease.

Subjects/Keywords: Chronic kidney disease; IgA nephropathy; mesangial cell; podocyte; CKAP4

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lassén, E. (2019). Molecular perspectives on glomerular cell physiology in chronic kidney disease. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/59539

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lassén, Emelie. “Molecular perspectives on glomerular cell physiology in chronic kidney disease.” 2019. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed February 27, 2021. http://hdl.handle.net/2077/59539.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lassén, Emelie. “Molecular perspectives on glomerular cell physiology in chronic kidney disease.” 2019. Web. 27 Feb 2021.

Vancouver:

Lassén E. Molecular perspectives on glomerular cell physiology in chronic kidney disease. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/2077/59539.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lassén E. Molecular perspectives on glomerular cell physiology in chronic kidney disease. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2019. Available from: http://hdl.handle.net/2077/59539

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Harvard University

24. Clark, Abbe Rose. Single-Cell Transcriptional Landscape of the Kidney Filter in Health and Disease.

Degree: PhD, 2019, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42106939

►

Progressive chronic kidney diseases (CKDs) affect more than 700 million people worldwide and are increasing in prevalence. However, the sequence of events resulting in CKD… (more)

Subjects/Keywords: kidney; podocyte; single-cell RNA sequencing; model; ctcf

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APA (6^th Edition):

Clark, A. R. (2019). Single-Cell Transcriptional Landscape of the Kidney Filter in Health and Disease. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:42106939

Chicago Manual of Style (16^th Edition):

Clark, Abbe Rose. “Single-Cell Transcriptional Landscape of the Kidney Filter in Health and Disease.” 2019. Doctoral Dissertation, Harvard University. Accessed February 27, 2021. http://nrs.harvard.edu/urn-3:HUL.InstRepos:42106939.

MLA Handbook (7^th Edition):

Clark, Abbe Rose. “Single-Cell Transcriptional Landscape of the Kidney Filter in Health and Disease.” 2019. Web. 27 Feb 2021.

Vancouver:

Clark AR. Single-Cell Transcriptional Landscape of the Kidney Filter in Health and Disease. [Internet] [Doctoral dissertation]. Harvard University; 2019. [cited 2021 Feb 27]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42106939.

Council of Science Editors:

Clark AR. Single-Cell Transcriptional Landscape of the Kidney Filter in Health and Disease. [Doctoral Dissertation]. Harvard University; 2019. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42106939

University of Western Ontario

25. Sull, Alexandra. The Role of Shroom3 in Kidney Development.

Degree: 2015, University of Western Ontario

URL: https://ir.lib.uwo.ca/etd/2881

► Chronic kidney disease (CKD) affects 10% of the population in industrialized nations. Recent genome wide association studies (GWAS) have correlated SHROOM3 with glomerular filtration rate… (more)

Subjects/Keywords: Shroom3; nephrogenesis; chronic kidney disease; actin; podocyte; mouse; Other Physiology

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APA (6^th Edition):

Sull, A. (2015). The Role of Shroom3 in Kidney Development. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/2881

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sull, Alexandra. “The Role of Shroom3 in Kidney Development.” 2015. Thesis, University of Western Ontario. Accessed February 27, 2021. https://ir.lib.uwo.ca/etd/2881.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sull, Alexandra. “The Role of Shroom3 in Kidney Development.” 2015. Web. 27 Feb 2021.

Vancouver:

Sull A. The Role of Shroom3 in Kidney Development. [Internet] [Thesis]. University of Western Ontario; 2015. [cited 2021 Feb 27]. Available from: https://ir.lib.uwo.ca/etd/2881.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sull A. The Role of Shroom3 in Kidney Development. [Thesis]. University of Western Ontario; 2015. Available from: https://ir.lib.uwo.ca/etd/2881

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

26. Li, Biao. Role of sFlt1 and Anxa2 in the Glomerular Filtration Barrier Integrity Maintenance.

Degree: PhD, 2016, University of Toronto

URL: http://hdl.handle.net/1807/89256

►

Gene targeting studies have confirmed the role of VEGF-VEGFR system in vasculogenesis and angiogenesis. While VEGFR2 is a mediator of major functions of VEGF, the… (more)

▼

Gene targeting studies have confirmed the role of VEGF-VEGFR system in vasculogenesis and angiogenesis. While VEGFR2 is a mediator of major functions of VEGF, the roles of VEGFR1 (Flt1) and its soluble isoform-sFlt1 are still elusive, they are thought of as decoy receptors for VEGF. However, accumulating studies revealed the physiological roles of sFlt1 in endothelial cells attachment, vascular sprouting and branching, and inhibition of VEGFR2 activation. Podocyte-specific knockout of Flt1 resulted in effacement of foot-processes and proteinuria, and one allele of tyrosine-kinase domain deleted Flt1 rescued this phenotype. Furthermore, exogenous sFlt1 promoted the attachment of podocyte and induced the formation of foot process-like structures. Mass spectrometry identified Anxa2 as a potential binding partner of sFlt1 on the podocyte membrane, and knockdown of Anxa2 in vitro caused drastic cytoskeletal changes in human podocytes. To further investigate the roles of sFlt1 and Anxa2 in the integrity maintenance of glomerular filtration barrier and the interactions between sFlt1 and Anxa2, we generated a transgenic sFlt1 floxed and a transgenic Anxa2 floxed mouse models. We set up the global sFlt1 KO (v1-/-) mouse line, and identified 17 novel sFlt isoforms from v1-/- mouse placentas by 3â -RACE where the major one was sFlt14-1 in place of sFlt1 (sFlt13) in wild type mice. We also confirmed that sinusoidal trophoblast giant cellsâ contribution to generation of these isoforms. Additionally, we showed that hypoxic signaling pathway and cleavage and polyadenylation alternative splicing machinery were also activated in v1-/- mice. We further confirmed that sFlt1 was essential for mouse embryogenesis and development and heart formation in a dose-dependent manner by generating 2 additional mouse models: 1) expressing ONLY the sFlt1 (Flt1TM-TK2); 2) expressing ONLY one-allele of sFlt1 (Flt1del/TM-TK-) on mixed genetic background (CD1 mouse). We generated global and podocyte-specific Anxa2 KO mouse lines, induced diabetes in global Anxa2 KO mice, and found that Anxa2 has an anti-glycation/glycosylation feature. Aged (1.5 years old) podocyte-specific Anxa2 KO mice developed proteinuria. PAS stain identified thick GBM and deposits in the sub-epithelial space. TEM confirmed these findings and demonstrated the intense darkness of the GBM, and further identified similar changes in younger mice (6-month old). The involvement of complement component C3 and other normal GBM components were not confirmed. In summary, these in vivo data provide the first genetic evidence that sFlt1, not full-length Flt1, is essential for mouse embryogenesis and growth and heart development in a dose-dependent manner; and that Flt1 has a large number of soluble isoforms in both human and mouse. In addition, Anxa2 from podocyte is actively involved in the cross-talk between podocyte and GBM.

2018-07-08 00:00:00

Advisors/Committee Members: Quaggin, Susan E, Medical Science.

Subjects/Keywords: angiogenesis; embryogenesis; podocyte; soluble VEGFR1; Vasculogenesis; VEGF; 0369

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Li, B. (2016). Role of sFlt1 and Anxa2 in the Glomerular Filtration Barrier Integrity Maintenance. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/89256

Chicago Manual of Style (16^th Edition):

Li, Biao. “Role of sFlt1 and Anxa2 in the Glomerular Filtration Barrier Integrity Maintenance.” 2016. Doctoral Dissertation, University of Toronto. Accessed February 27, 2021. http://hdl.handle.net/1807/89256.

MLA Handbook (7^th Edition):

Li, Biao. “Role of sFlt1 and Anxa2 in the Glomerular Filtration Barrier Integrity Maintenance.” 2016. Web. 27 Feb 2021.

Vancouver:

Li B. Role of sFlt1 and Anxa2 in the Glomerular Filtration Barrier Integrity Maintenance. [Internet] [Doctoral dissertation]. University of Toronto; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1807/89256.

Council of Science Editors:

Li B. Role of sFlt1 and Anxa2 in the Glomerular Filtration Barrier Integrity Maintenance. [Doctoral Dissertation]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/89256

Freie Universität Berlin

27. Müller, Tilman. Apelinerges System in der Niere: Implikationen für die diabetische Nierenerkrankung.

Degree: 2020, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-27613

► Für die bioaktiven Peptide des apelinergen Systems und ihres Rezeptors APJ wurden in experimentellen kardiovaskulären Erkrankungen und der diabetischen Nierenkrankheit (DKD) eine protektive Rolle aufgezeigt.… (more)

▼ Für die bioaktiven Peptide des apelinergen Systems und ihres Rezeptors APJ wurden in experimentellen kardiovaskulären Erkrankungen und der diabetischen Nierenkrankheit (DKD) eine protektive Rolle aufgezeigt. Die Mechanismen dieses renoprotektiven Effektes konnten jedoch noch nicht aufgeklärt werden. In dieser Studie untersuchten wir die Lokalisation von APJ in normalem Nierengewebe und seine Expression in dem db/db Modell der DKD. Weiterhin wurde der Effekt von Hyperglykämie und Angiotensin II auf APJ in kultivierten Podozyten analysiert. Im Glomerulus wurde Ko-lokalisation von APJ mit Markern für Podozyten gefunden, allerdings nicht mit Markern für endotheliale Zellen. Stimulation mit Pyr1Apelin-13 führte in Podozyten nach 15 Minuten zu Veränderungen im Phosphorylierungsstatus der Signalproteine AKT, ERK und p70S6K. Pyr1Apelin-13 senkte die Aktivität von Caspase-3 und NADPH-Oxidase in Podozyten gezüchtet in hochglukosigem Nährmedium, was den anti-apoptotischen und anti-oxidativen Effekt von APJ Stimulation widerspiegelt. In Podozyten im hochglukosigen Medium wurde eine Herunterregulierung der APJ mRNA im Vergleich zu normoglykämen Bedingungen gefunden und Applikation von Angiotensin II führte zu einer noch weiteren Senkung. Im Vergleich zu den db/m Kontrollen waren APJ und Präproapelin mRNA in Nieren von db/db Mäusen deutlich gesenkt einhergehend mit reduzierten tubulären APJ Protein Leveln nachgewiesen mittels Western Blot und Immunfärbung. Zusammengefasst zeigt sich das apelinerge System herunterreguliert in Nieren von db/db Mäusen. Innerhalb des Glomerulus ist APJ vor allem in den Podozyten lokalisiert und hebt hier nach Stimulation mit Pyr1Apelin-13 den pro-apoptotischen und pro-oxidativen Effekt von Hyperglykämie auf. Dies könnte auf eine potentielle therapeutische Nutzung von Apelin und Agonisten mit verlängerter Halbwertszeit für die Therapie von DKD hindeuten. Advisors/Committee Members: male (gender), N.N. (firstReferee), N.N. (furtherReferee).

Subjects/Keywords: Apelin; diabetic kidney disease; Podocyte; APJ; Apelinergic System; ddc:610

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Müller, T. (2020). Apelinerges System in der Niere: Implikationen für die diabetische Nierenerkrankung. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-27613

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Müller, Tilman. “Apelinerges System in der Niere: Implikationen für die diabetische Nierenerkrankung.” 2020. Thesis, Freie Universität Berlin. Accessed February 27, 2021. http://dx.doi.org/10.17169/refubium-27613.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Müller, Tilman. “Apelinerges System in der Niere: Implikationen für die diabetische Nierenerkrankung.” 2020. Web. 27 Feb 2021.

Vancouver:

Müller T. Apelinerges System in der Niere: Implikationen für die diabetische Nierenerkrankung. [Internet] [Thesis]. Freie Universität Berlin; 2020. [cited 2021 Feb 27]. Available from: http://dx.doi.org/10.17169/refubium-27613.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Müller T. Apelinerges System in der Niere: Implikationen für die diabetische Nierenerkrankung. [Thesis]. Freie Universität Berlin; 2020. Available from: http://dx.doi.org/10.17169/refubium-27613

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

28. Koop, Klaas. Proteinuria and function loss in native and transplanted kidneys.

Degree: 2009, Department of Pathology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University

URL: http://hdl.handle.net/1887/13951

► “Bones can break, muscles can atrophy, glands can loaf, even the brain can go to sleep, without immediately endangering our survival, but when the kidneys… (more)

Subjects/Keywords: Glomerulus; Kidney; Proteinuria; Podocyte; Transplantation; Cyclosporine; Glomerulus; Kidney; Proteinuria; Podocyte; Transplantation; Cyclosporine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Koop, K. (2009). Proteinuria and function loss in native and transplanted kidneys. (Doctoral Dissertation). Department of Pathology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University. Retrieved from http://hdl.handle.net/1887/13951

Chicago Manual of Style (16^th Edition):

Koop, Klaas. “Proteinuria and function loss in native and transplanted kidneys.” 2009. Doctoral Dissertation, Department of Pathology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University. Accessed February 27, 2021. http://hdl.handle.net/1887/13951.

MLA Handbook (7^th Edition):

Koop, Klaas. “Proteinuria and function loss in native and transplanted kidneys.” 2009. Web. 27 Feb 2021.

Vancouver:

Koop K. Proteinuria and function loss in native and transplanted kidneys. [Internet] [Doctoral dissertation]. Department of Pathology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University; 2009. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1887/13951.

Council of Science Editors:

Koop K. Proteinuria and function loss in native and transplanted kidneys. [Doctoral Dissertation]. Department of Pathology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University; 2009. Available from: http://hdl.handle.net/1887/13951

Universidade do Rio Grande do Sul

29. Nascimento, Jonathan Fraportti do. Expressão gênica de proteínas do podócito na urina de pacientes diabéticos normo, micro ou macroalbuminúricos e em pré diabeticos.

Degree: 2012, Universidade do Rio Grande do Sul

URL: http://hdl.handle.net/10183/142953

►

Introdução: A lesão do podócito exerce um papel crítico na nefropatia diabética (ND) e é um fator preditivo de albuminúria patológica e progressão da doença.… (more)

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Introdução: A lesão do podócito exerce um papel crítico na nefropatia diabética (ND) e é um fator preditivo de albuminúria patológica e progressão da doença. Neste estudo foi avaliada a expressão gênica de proteínas associadas ao podócito na urina de pacientes diabéticos em diferentes estágios da ND e em indivíduos com pré diabetes. Material e Métodos: Foram estudados 67 pacientes diabéticos com normo (n=34), micro (n=14) ou macroalbuminúria (n=19), dezenove indivíduos pré diabéticos e 15 controles saudáveis. O RNAm de nefrina, podocina, podocalixina, sinaptopodina, Transient Receptor Potential Cation Channel 6 (TRPC6), alfa actinina-4 e TGF1 foi quantificado por PCR em tempo real (2-ΔΔCt) em células do sedimento urinário. A expressão dos genes alvo do podócito foi correlacionada com albuminúria, controle glicêmico e função renal. O desempenho diagnóstico dos genes para albuminúria patológica foi determinado por curva ROC, e o seu efeito independente sobre esse desfecho foi avaliado por análise de regressão de Poisson. Resultados: O RNAm na urina dos genes alvo foi significativamente maior nos pacientes diabéticos em comparação aos não diabéticos, exceto de sinaptopodina e TGFβ1. A expressão de nefrina foi mais elevada nos indivíduos diabéticos micro e macroalbuminúricos comparado aos controles (p=0,04 e p<0,001 respectivamente), pré diabéticos (p<0,05) e normoalbuminúricos (p<0,05). Embora sua expressão tenha sido maior do que nos não diabéticos, os genes TRPC6, podocalixina e alfa actinina-4 não discriminaram os estágios da ND. A correlação da expressão dos genes com albuminúria e hemoglobina glicada foi estatisticamente significativa. Pacientes pré diabéticos tiveram expressão gênica semelhante aos controles. Na análise multivariada, apenas o gene da nefrina foi preditivo de albuminúria patológica. 6 Conclusões: A expressão das proteínas associadas ao podócito na urina foi maior nos pacientes diabéticos, mas não houve correlação direta do RNAm dos genes com níveis crescentes de albuminúria, exceto de nefrina. O gene da nefrina foi o único que discriminou os diferentes estágios da ND e foi preditivo de albuminúria patológica, mas a podocalixina e o TRPC6 também se correlacionaram com albuminúria e controle glicêmico. Neste estudo preliminar não se identificou aumento da expressão gênica das proteínas do podócito na urina em indivíduos com pré diabetes.

Introduction: Podocyte damage plays a critical role in the development of diabetic nephropathy (DN). The present study evaluated gene expression of podocyte-associated proteins in urine of pre-diabetic and diabetic patients at different stages of DN. Material and Methods: We studied 19 pre-diabetic patients, 67 diabetic patients with normo (n = 34), micro (n = 15), or macroalbuminuria (n = 19), and 15 healthy controls. Levels of mRNA of nephrin, podocin, podocalyxin, synaptopodin, transient receptor potential cation channel 6 (TRPC6), alpha-actinin-4, and TGF-1 were quantitatively measured by real-time polymerase chain reaction in urinary sediment. Gene…

Advisors/Committee Members: Veronese, Francisco José Veríssimo.

Subjects/Keywords: Diabetes mellitus; Podocyte; TRPC6; Podócitos; Expressão gênica; Podocin; Nephrin; Urina; Pre-diabetes; Albuminúria; Diabetic nephropathy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nascimento, J. F. d. (2012). Expressão gênica de proteínas do podócito na urina de pacientes diabéticos normo, micro ou macroalbuminúricos e em pré diabeticos. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/142953

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nascimento, Jonathan Fraportti do. “Expressão gênica de proteínas do podócito na urina de pacientes diabéticos normo, micro ou macroalbuminúricos e em pré diabeticos.” 2012. Thesis, Universidade do Rio Grande do Sul. Accessed February 27, 2021. http://hdl.handle.net/10183/142953.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nascimento, Jonathan Fraportti do. “Expressão gênica de proteínas do podócito na urina de pacientes diabéticos normo, micro ou macroalbuminúricos e em pré diabeticos.” 2012. Web. 27 Feb 2021.

Vancouver:

Nascimento JFd. Expressão gênica de proteínas do podócito na urina de pacientes diabéticos normo, micro ou macroalbuminúricos e em pré diabeticos. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2012. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10183/142953.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nascimento JFd. Expressão gênica de proteínas do podócito na urina de pacientes diabéticos normo, micro ou macroalbuminúricos e em pré diabeticos. [Thesis]. Universidade do Rio Grande do Sul; 2012. Available from: http://hdl.handle.net/10183/142953

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

30. Rezende, Gabriela de Mendonça. Lesão podocitária na nefrite lúpica membranosa pura e proliferativa: mecanismos distintos de proteinúria?.

Degree: PhD, Processos Imunes e Infecciosos, 2015, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/5/5164/tde-13052015-093352/ ;

►

Proteinúria é a principal manifestação da nefrite lúpica (NL) e reflete lesão no podócito. Análise dos biomarcadores do podócito foi realizada com o objetivo de… (more)

▼

Proteinúria é a principal manifestação da nefrite lúpica (NL) e reflete lesão no podócito. Análise dos biomarcadores do podócito foi realizada com o objetivo de identificar se o fenótipo podocitário é distinto na NL membranosa pura e proliferativa. Expressão de sinaptopodina, proteína 1 do tumor de Wilms (Wilms tumor protein 1 - WT1), proteína epitelial glomerular 1 (glomerular epitelial protein 1 - GLEPP1) e nefrina foi avaliada em 52 biópsias de NL por imunohistoquímica. Expressão preservada de sinaptopodina foi observada em apenas 10 (19,2%) de todas as biópsias enquanto que 42 (80,8%) apresentavam expressão reduzida. Ambos os grupos tinham proteinúria semelhante no momento da biópsia (p = 0,22), porém, no seguimento médio de quatro anos houve uma tendência para menores níveis médios de proteinúria nos pacientes com marcação preservada de sinaptopodina (0,26 ± 0,23 vs 0,84 ± 0,90 g/24 h, p = 0,05) do que naqueles com expressão reduzida. Trinta e nove (75%) biópsias foram classificadas como proliferativa e treze (25%) como membranosa pura. Comparação dos biomarcadores do podócito demonstrou predomíno de marcação preservada de sinaptopodina (69,2%), WT1 (69,2%), GLEPP1 (53,9%) e nefrina (60%) no grupo membranosa pura enquanto apenas < 10% das proliferativas apresentaram expressão preservada. Nossos dados sugerem que nas classes proliferativas parece haver lesão estrutural do podócito, enquanto que na membranosa pura o padrão predominantemente preservado sugere uma lesão funcional do podócito que pode ser responsável pelo melhor prognóstico a longo prazo do desfecho da proteinúria

Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte injury. Analysis of podocyte biomarkers was performed attempting to identify if podocyte phenotype is distinct in pure membranous and proliferative LN. Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by immunohistochemistry. Preserved synaptopodin expression was observed in only 10 (19,2%) of all biopsies while 42 (80,8%) had a reduced expression. Both groups had comparable proteinuria at the time of biopsy (p=0,22), however, in the mean follow-up of four years there was a tendency to lower mean levels of proteinuria in patients with preserved synaptopodin staining (0,26 ± 0,23 vs. 0,84 ± 0,90 g/24 h, p=0,05) than those with diminished expression. Thirty-nine (75%) biopsies were classified as proliferative and thirteen (25%) as pure membranous. Comparison of podocyte biomarkers demonstrated a predominance of preserved staining of synaptopodin (69,2%), WT1 (69,2%), GLEPP1 (53,9%) and nephrin (60%) in the pure membranous group whereas only < 10% of the proliferative showed preserved expression. Our data suggest that in proliferative forms there seems to occur structural podocyte damage, whereas in the pure membranous the predominant preserved pattern suggests a dysfunctional podocyte lesion that may account for the better long-term prognosis of proteinuria outcome

Advisors/Committee Members: Bonfa, Eloisa Silva Dutra de Oliveira.

Subjects/Keywords: Lúpus eritematoso sistêmico; Lupus nephritis; Nefrite lúpica; Podócito; Podocyte; Proteinuria; Proteinúria; Systemic lupus erythematosus

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APA (6^th Edition):

Rezende, G. d. M. (2015). Lesão podocitária na nefrite lúpica membranosa pura e proliferativa: mecanismos distintos de proteinúria?. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/5/5164/tde-13052015-093352/ ;

Chicago Manual of Style (16^th Edition):

Rezende, Gabriela de Mendonça. “Lesão podocitária na nefrite lúpica membranosa pura e proliferativa: mecanismos distintos de proteinúria?.” 2015. Doctoral Dissertation, University of São Paulo. Accessed February 27, 2021. http://www.teses.usp.br/teses/disponiveis/5/5164/tde-13052015-093352/ ;.

MLA Handbook (7^th Edition):

Rezende, Gabriela de Mendonça. “Lesão podocitária na nefrite lúpica membranosa pura e proliferativa: mecanismos distintos de proteinúria?.” 2015. Web. 27 Feb 2021.

Vancouver:

Rezende GdM. Lesão podocitária na nefrite lúpica membranosa pura e proliferativa: mecanismos distintos de proteinúria?. [Internet] [Doctoral dissertation]. University of São Paulo; 2015. [cited 2021 Feb 27]. Available from: http://www.teses.usp.br/teses/disponiveis/5/5164/tde-13052015-093352/ ;.

Council of Science Editors:

Rezende GdM. Lesão podocitária na nefrite lúpica membranosa pura e proliferativa: mecanismos distintos de proteinúria?. [Doctoral Dissertation]. University of São Paulo; 2015. Available from: http://www.teses.usp.br/teses/disponiveis/5/5164/tde-13052015-093352/ ;

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