subject:(renal dysplasia)

McMaster University

1. Cunanan, Joanna. Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia.

Degree: MSMS, 2019, McMaster University

URL: http://hdl.handle.net/11375/24793

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M.Sc. Thesis Dissertation, August 2019, McMaster University

Renal dysplasia, defined as the abnormal development of kidney tissue, is the leading cause of kidney disease in… (more)

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M.Sc. Thesis Dissertation, August 2019, McMaster University

Renal dysplasia, defined as the abnormal development of kidney tissue, is the leading cause of kidney disease in children. While there are numerous causes of renal dysplasia (i.e. genetic, environmental and epigenetic factors), there is no cure to this abnormal defect. Kidney development occurs by two main processes: branching morphogenesis, which forms the collecting duct system, and nephrogenesis, which generates the nephrons, the functional units of the kidney. Our previous studies have demonstrated that β-catenin, a dual-function protein involved in cell adhesion and gene transcription, regulates branching morphogenesis and nephrogenesis. Furthermore, we discovered that nuclear β-catenin levels are increased in kidneys from patients with renal dysplasia, suggesting β-catenin can be a potential therapeutic target to modulate kidney development and renal dysplasia. Quercetin is a flavonoid that reduces β-catenin levels and inhibits its transcriptional activity, leading to improved outcomes in cancer and in kidney fibrosis. The role of quercetin in kidney development and in abnormal defects that arise during kidney development is yet to be examined. Using embryonic mouse kidney organ culture, I found that quercetin treatment resulted in a dose-dependent disruption in branching morphogenesis and nephrogenesis. In addition, quantitative reverse-transcriptase PCR revealed a decreased expression of β-catenin target genes essential for kidney development (i.e. Pax2, Six2 and GDNF). Immunohistochemistry for β-catenin demonstrated that quercetin reduced nuclear β-catenin expression and increased cytoplasmic and membrane-bound expression in a dose-dependent manner. These results were confirmed by Western blot analysis. These novel findings demonstrate that quercetin treatment resulted in decreased levels of nuclear β-catenin, resulting in a decrease in its transcriptional activity which manifested in alterations in kidney developmental processes, suggesting quercetin is effective at reducing nuclear β-catenin in wild-type embryonic kidneys. Next, to determine whether quercetin has any effects on renal dysplasia, I utilized transgenic mice models that overexpress β-catenin in select cells of the embryonic kidney. These models recapitulate the defects observed in human renal dysplasia, including disorganized branching morphogenesis and disrupted nephrogenesis. Quercetin treatment of embryonic dysplastic kidneys resulted in a partial rescue of renal dysplasia which was evident in marked improvements in branching morphogenesis and nephrogenesis, as well as an increase in the number of properly-developing nephrons in the kidney tissue. Analysis of β-catenin expression in quercetin-treated dysplastic kidneys revealed a decrease in nuclear levels and an increase in cytoplasmic and membrane-bound levels, resulting in a reduced expression of target genes (Pax2, Six2, and GDNF). Finally, this partial rescue of renal dysplasia was associated with an improved and organized…

Advisors/Committee Members: Bridgewater, Darren, Medical Sciences (Growth and Development).

Subjects/Keywords: kidney development; beta-catenin; renal dysplasia; quercetin

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

APA (6^th Edition):

Cunanan, J. (2019). Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/24793

Chicago Manual of Style (16^th Edition):

Cunanan, Joanna. “Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia.” 2019. Masters Thesis, McMaster University. Accessed February 27, 2021. http://hdl.handle.net/11375/24793.

MLA Handbook (7^th Edition):

Cunanan, Joanna. “Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia.” 2019. Web. 27 Feb 2021.

Vancouver:

Cunanan J. Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia. [Internet] [Masters thesis]. McMaster University; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/11375/24793.

Council of Science Editors:

Cunanan J. Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia. [Masters Thesis]. McMaster University; 2019. Available from: http://hdl.handle.net/11375/24793

University of Adelaide

2. Goel, Pranay. Characterisation of pathophysiological function of NEDD4-2 in kidney.

Degree: 2016, University of Adelaide

URL: http://hdl.handle.net/2440/109813

► Nedd4-2 (NEDD4L, neural precursor cell expressed, developmentally down regulated 4-like) belongs to the Nedd4 family of ubiquitin ligases. These ligases aid in maintaining cellular homeostasis… (more)

▼ Nedd4-2 (NEDD4L, neural precursor cell expressed, developmentally down regulated 4-like) belongs to the Nedd4 family of ubiquitin ligases. These ligases aid in maintaining cellular homeostasis by binding to, and ubiquitinating a number of membrane proteins to initiate their internalization and turnover. Previous work from our laboratory has suggested that Nedd4-2 plays an essential role in regulating ion channels, especially the epithelial sodium channel and voltage gated sodium channels. The misregulation of these channels has been implicated in multiple channelopathies, including hypertension and cystic fibrosis like disease. This study characterises a previously unknown function of Nedd4-2 in the kidney. In order to understand this significance of Nedd4-2 in renal homeostasis, the previously generated Nedd4-2⁻ʹ⁻ (Nedd4-2 knockout) mice (Boase et al., 2011) were characterised. The initial histological examination of postnatal kidneys suggested renal cyst formation in Nedd4-2⁻ʹ⁻ animals. Further analysis revealed that Nedd4-2 loss results in renal dysplasia. Nedd4-2⁻ʹ⁻ mice showed variable renal cystic index, onset of cyst formation starting from postnatal day 2 and progressing until the Nedd4-2⁻ʹ⁻ animals die due to respiratory distress around day 19-21. To investigate the prevalence of the cystic phenotype in other tissues histological analysis was performed in pancreas, liver, spleen, colon, stomach and thymus with no significant pathological differences observed in the knockout mice. The Nedd4-2⁻ʹ⁻ kidneys showed increased cell proliferation, with no apoptotic differences in the cells lining the cystic epithelia suggesting an imbalance between cell proliferation and apoptosis in cyst formation. The cyst formation and kidney development disorders are associated with malformation in the kidney tissue leading to extracellular matrix modification with enhanced accumulation of collagens causing increased interstitial fibrosis. The Nedd4-2⁻ʹ⁻ kidneys showed increased interstitial fibrosis, collagen-1 accumulation and expression during progression of the disease. The renal tissue membrane is made up of polysaccharides, glycogen and mucin, the Nedd4-2⁻ʹ⁻ kidneys were found to have decreased accumulation of polysaccharides. The cysts in the Nedd4-2⁻ʹ⁻ kidneys originated from different parts within the nephron. The larger cysts originated from loop of Henle and with the smaller cysts from collecting ducts and distal convoluted tubules. The cystic progression is dependent on cAMP flux initiated by fluid secretion within the cyst. The postnatal day 19 cystic kidneys in Nedd4-2⁻ʹ⁻ animals showed increased cAMP levels suggesting cystic disease progression. As renal cystic disorders may arise from abnormal cilia, ciliary anomalies were found in the Nedd4-2⁻ʹ⁻ around the cysts suggesting importance of cilia in kidney cyst formation. Polycystins are known to be involved in renal cyst development with polycystin-1 and polycystin-2 together known to form calcium ion channel. To investigate the role of Nedd4-2 in the regulation of… Advisors/Committee Members: Kumar, Sharad (advisor), Dorstyn, Loretta Esterina (advisor), School of Medicine (school).

Subjects/Keywords: ubiquitin ligases; Polycystic Kidney Disease; renal dysplasia; kidney; ion channels; Polycystins; cysts; apoptosis; proliferation; fibrosis; Research by Publication

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

APA (6^th Edition):

Goel, P. (2016). Characterisation of pathophysiological function of NEDD4-2 in kidney. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/109813

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):

Goel, Pranay. “Characterisation of pathophysiological function of NEDD4-2 in kidney.” 2016. Thesis, University of Adelaide. Accessed February 27, 2021. http://hdl.handle.net/2440/109813.

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

MLA Handbook (7^th Edition):

Goel, Pranay. “Characterisation of pathophysiological function of NEDD4-2 in kidney.” 2016. Web. 27 Feb 2021.

Vancouver:

Goel P. Characterisation of pathophysiological function of NEDD4-2 in kidney. [Internet] [Thesis]. University of Adelaide; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/2440/109813.

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

Council of Science Editors:

Goel P. Characterisation of pathophysiological function of NEDD4-2 in kidney. [Thesis]. University of Adelaide; 2016. Available from: http://hdl.handle.net/2440/109813

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

3. van Twist, Daan. The renin-angiotensin system in the hypertensive kidney: clinical studies in patients with essential hypertension, fibromuscular dysplasia, and the atherosclerotic renal artery stenosis.

Degree: 2016, NARCIS

URL: https://cris.maastrichtuniversity.nl/en/publications/4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; urn:nbn:nl:ui:27-4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; 4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; urn:nbn:nl:ui:27-4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; https://cris.maastrichtuniversity.nl/en/publications/4033f930-b9c4-4e9c-8465-1cf118a0cb3d

► The renin-angiotensin system is one of the most important systems for regulating blood pressure. Various signal compounds (angiotensins) play a crucial role in this system.… (more)

Subjects/Keywords: hypertension; renin-angiotensin system; fibromuscular dysplasia; atherosclerosis; renal artery stenosis

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

APA (6^th Edition):

van Twist, D. (2016). The renin-angiotensin system in the hypertensive kidney: clinical studies in patients with essential hypertension, fibromuscular dysplasia, and the atherosclerotic renal artery stenosis. (Doctoral Dissertation). NARCIS. Retrieved from https://cris.maastrichtuniversity.nl/en/publications/4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; urn:nbn:nl:ui:27-4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; 4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; urn:nbn:nl:ui:27-4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; https://cris.maastrichtuniversity.nl/en/publications/4033f930-b9c4-4e9c-8465-1cf118a0cb3d

Chicago Manual of Style (16^th Edition):

van Twist, Daan. “The renin-angiotensin system in the hypertensive kidney: clinical studies in patients with essential hypertension, fibromuscular dysplasia, and the atherosclerotic renal artery stenosis.” 2016. Doctoral Dissertation, NARCIS. Accessed February 27, 2021. https://cris.maastrichtuniversity.nl/en/publications/4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; urn:nbn:nl:ui:27-4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; 4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; urn:nbn:nl:ui:27-4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; https://cris.maastrichtuniversity.nl/en/publications/4033f930-b9c4-4e9c-8465-1cf118a0cb3d.

MLA Handbook (7^th Edition):

van Twist, Daan. “The renin-angiotensin system in the hypertensive kidney: clinical studies in patients with essential hypertension, fibromuscular dysplasia, and the atherosclerotic renal artery stenosis.” 2016. Web. 27 Feb 2021.

Vancouver:

van Twist D. The renin-angiotensin system in the hypertensive kidney: clinical studies in patients with essential hypertension, fibromuscular dysplasia, and the atherosclerotic renal artery stenosis. [Internet] [Doctoral dissertation]. NARCIS; 2016. [cited 2021 Feb 27]. Available from: https://cris.maastrichtuniversity.nl/en/publications/4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; urn:nbn:nl:ui:27-4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; 4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; urn:nbn:nl:ui:27-4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; https://cris.maastrichtuniversity.nl/en/publications/4033f930-b9c4-4e9c-8465-1cf118a0cb3d.

Council of Science Editors:

van Twist D. The renin-angiotensin system in the hypertensive kidney: clinical studies in patients with essential hypertension, fibromuscular dysplasia, and the atherosclerotic renal artery stenosis. [Doctoral Dissertation]. NARCIS; 2016. Available from: https://cris.maastrichtuniversity.nl/en/publications/4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; urn:nbn:nl:ui:27-4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; 4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; urn:nbn:nl:ui:27-4033f930-b9c4-4e9c-8465-1cf118a0cb3d ; https://cris.maastrichtuniversity.nl/en/publications/4033f930-b9c4-4e9c-8465-1cf118a0cb3d

4. Μητσιώνη, Άρτεμις. Μελέτη γονιδίων που εμπλέκονται στις συγγενείς ανωμαλίες του ουροποιητικού (CAKUT).

Degree: 2012, University of Ioannina; Πανεπιστήμιο Ιωαννίνων

URL: http://hdl.handle.net/10442/hedi/29296

► IntroductionCongenital anomalies of kidney and urinary tract account for almost 0,5% of all pregnancies and are the most often cause of chronic kidney disease in… (more)

▼ IntroductionCongenital anomalies of kidney and urinary tract account for almost 0,5% of all pregnancies and are the most often cause of chronic kidney disease in infants and young children. About 30-40% of children with chronic renal disease or end stage renal disease have congenital anomalies of kidney and urinary tract. One of the most frequent is vesico-ureteric reflux (VUR), which is often accompanied by renal hypodysplasia (VUR-RHD). To date, the heritability and the pathogenesis of these anomalies has not been established. ROBO2 gene is involved during nephrogenesis at the early stage of the ureteric bud induction. However, in the literature it is not clear if the gene is implicated in the pathogenesis of VUR.ObjectivesThe aim of the present study is to evaluate the presence of sequence variations in the ROBO2 gene in children with VUR and VUR-RHD. In silico evaluation was also performed for factors that can epigenetically affect the gene’s expression.Materials and MethodsA total of 103 pediatric patients were studied: 65 with VUR (10 familial VUR) and 38 with VUR-RHD. A control group of 200 healthy children, age and sex matched with the patients were also screened.The gene screening was performed by single strand conformation polymorphism (SSCP) or multiple restriction fragment (MRF)-SSCP electrophoresis, in two different running conditions. Subsequently the samples with variations were characterized by direct DNA sequencing. The control group was screened using restriction enzymes or MRF-SSCP. Statistical analysis (chi-square test) was carried out as well as in silico analysis for the nucleotide changes that were found (ESEfinder and SplicePort). In silico analysis was also performed regarding the content of the gene in CpG islands (EMBOSS CpGPlot), the homology with miRNAs (miRBase) and the content in transposable elements (UCSC Genome Bioinformatics, RepeatMasker).Results The Single Nucleotide Polymorphisms (SNPs) IVS1-53G>A (rs9874095) and IVS5-31A>G (rs76571990) were found. Statistical analysis for IVS1-53G>A showed a significance difference toward the control group and in silico analysis showed that the SNP does not affect mRNA splicing. The second SNP, IVS1-53G>A, is reported for the first time, even though it is already recorded, and was detected only in one of the patients. In silico results demonstrated an alteration in two SR proteins’ binding (ESEfinder) and two additional acceptor sites (SplicePort), exhibiting a high possibility for the splice site to be affected. The gene has eight CpG islands >200 nucleotides long. The sequence of the gene displays homology with 17 mature miRNAs and 60 pre-miRNAs. Higher score and e-value<0,1 had 3 mature miRNAs and 25 pre-miRNAs. The alignment with the mature miRNAs has a difference from 1-3 bases, whereas with the pre-miRNAs >10 bases. Also the sequence of the gene has a content of 25,9% in transposable elements, including DNA transposons (4,55%), although the last do not participle in any biological procedure, until today. ConclusionsThe results so far…

Subjects/Keywords: Συγγενείς ανωμαλίες του ουροποιητικού συστήματος; Γονίδιο ROBO2; Μεταλλάξεις; Νεφρογένεση; Κυστεοουρητηρική παλινδρόμηση; Νεφρική υποπλασία/δυσπλασία; Βιοπληροφορική ανάλυση; Congenital anomalies of kidney and urinary tract; ROBO2 gene; Mutations; Nephrogenesis; Vesicoureteric reflux; Renal hypoplasia/dysplasia; Bioinformatic analysis

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

APA (6^th Edition):

Μητσιώνη, . �. (2012). Μελέτη γονιδίων που εμπλέκονται στις συγγενείς ανωμαλίες του ουροποιητικού (CAKUT). (Thesis). University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Retrieved from http://hdl.handle.net/10442/hedi/29296

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):

Μητσιώνη, Άρτεμις. “Μελέτη γονιδίων που εμπλέκονται στις συγγενείς ανωμαλίες του ουροποιητικού (CAKUT).” 2012. Thesis, University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Accessed February 27, 2021. http://hdl.handle.net/10442/hedi/29296.

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

MLA Handbook (7^th Edition):

Μητσιώνη, Άρτεμις. “Μελέτη γονιδίων που εμπλέκονται στις συγγενείς ανωμαλίες του ουροποιητικού (CAKUT).” 2012. Web. 27 Feb 2021.

Vancouver:

Μητσιώνη �. Μελέτη γονιδίων που εμπλέκονται στις συγγενείς ανωμαλίες του ουροποιητικού (CAKUT). [Internet] [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2012. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10442/hedi/29296.

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

Council of Science Editors:

Μητσιώνη �. Μελέτη γονιδίων που εμπλέκονται στις συγγενείς ανωμαλίες του ουροποιητικού (CAKUT). [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2012. Available from: http://hdl.handle.net/10442/hedi/29296

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

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