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You searched for +publisher:"Temple University" +contributor:("Susztak, Katalin;"). Showing records 1 – 2 of 2 total matches.

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Temple University

1. YANG, JI YEON. CD40 monocyte differentiation mediates tissue inflammation in chronic kidney disease.

Degree: PhD, 2015, Temple University

Pharmacology

Patients with chronic kidney disease (CKD) develop hyperhomocysteinemia (HHcy), have increased inflammatory monocytes (MC) and 10-times higher cardiovascular mortality than the general population. Here, we investigated HHcy-related MC differentiation in CKD. Twenty seven CKD and CVD, and 14 healthy subjects were recruited. CD40 was selected as a CKD-induced MC activation marker by mining for CKD-MC-mRNA screen database. We found that CD14++CD16+ MC, often denoted as inflammatory subset, soluble CD40 ligand (sCD40L), and TNFα/IL-6 levels were augmented in CVD and CKD subjects. CD40hiCD14++CD16+ MC, plasma homocysteine (Hcy) and S-adenosylhomocysteine (SAH) levels were increased in CVD and further elevated in CKD subjects. In cultured human peripheral blood mononuclear cells, CKD patient serum, Hcy, CD40L and TNFα/IL-6 induced CD40hiCD14++CD16+ MC differentiation, which was prevented by Hcy-lowering folic acid and neutralizing antibodies against TNFα and IL-6. Interestingly, CD14++CD16+ and CD40hiCD14++CD16+ MCs were negatively correlated with plasma S-adenosylmethionine/SAH (SAM/SAH) ratios, an indicator of methylation status, in CKD and CVD subjects. In white blood cells (WBC) isolated from CKD and CVD subjects with lower SAM/SAH ratios, hypomethylation was identified on the CG pair of NFκB consensus element in the core promoter located at the CpG island of CD40 gene by DNA methylation mapping using bisulfite converting pyrosequencing. Moreover, Hcy inhibited DNA methyltransferase-1 activity in cultured human blood MC. In conclusion, HHcy induces CD14++CD16+ and CD40hiCD14++CD16+ MC differentiation, at least in part, via sCD40L induction and CD40 DNA hypomethylation in CKD and CVD subjects. To study the role of CD40 in the development of kidney pathology and vascular disease, we then established mouse model of CKD-induced CVD (5/6 nephrectomy CKD model plus left carotid artery ligation) in CD40-/- mice. Bone marrow (BM)-derived cells were traced by the transplantation of BM cells from enhanced green fluorescent protein (EGFP) transgenic CD40+/+ mice after sublethal irradiation of the recipient CD40-/- mice. We demonstrated here that CKD accelerated carotid artery atherosclerosis, exacerbated metabolism, increased spleen weight and circulating CD40+ inflammatory MC, and further increased differentiation of mononuclear phagocytic cells (MPC); CD11b+F4/80- MC, CD11b+F4/80+ macrophage (Mϕ) and CD11c+CD11b+F4/80+ bone marrow-derived dendritic cell in the kidney and aorta, which were abolished by CD40-/- mice. We also found that CKD kidney elevated CD40 expression and induced MC chemotactic signals; CCL2, CCL12, and CCL5 chemokines, which were abolished in CD40-/- mice. In conclusion, our results suggest that CD40 induction in the chronic kidney disease mediates kidney chemokine production, which in turn contributes to acceleration of myeloid cell infiltration, MPC differentiation, and carotid artery atherosclerosis.

Temple University – Theses

Advisors/Committee Members: Wang, Hong, Yang, Xiao-Feng;, Ashby, Barrie, Gallucci, Stefania, Merali, Salim, Susztak, Katalin;.

Subjects/Keywords: Medicine;

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

APA (6th Edition):

YANG, J. Y. (2015). CD40 monocyte differentiation mediates tissue inflammation in chronic kidney disease. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,349139

Chicago Manual of Style (16th Edition):

YANG, JI YEON. “CD40 monocyte differentiation mediates tissue inflammation in chronic kidney disease.” 2015. Doctoral Dissertation, Temple University. Accessed April 14, 2021. http://digital.library.temple.edu/u?/p245801coll10,349139.

MLA Handbook (7th Edition):

YANG, JI YEON. “CD40 monocyte differentiation mediates tissue inflammation in chronic kidney disease.” 2015. Web. 14 Apr 2021.

Vancouver:

YANG JY. CD40 monocyte differentiation mediates tissue inflammation in chronic kidney disease. [Internet] [Doctoral dissertation]. Temple University; 2015. [cited 2021 Apr 14]. Available from: http://digital.library.temple.edu/u?/p245801coll10,349139.

Council of Science Editors:

YANG JY. CD40 monocyte differentiation mediates tissue inflammation in chronic kidney disease. [Doctoral Dissertation]. Temple University; 2015. Available from: http://digital.library.temple.edu/u?/p245801coll10,349139


Temple University

2. Xiong, Xinyu. Carom, a novel gene, is up-regulated by homocysteine through DNA hypomethylation to inhibit endothelial cell migration and angiogenesis.

Degree: PhD, 2014, Temple University

Pharmacology

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD). We previously demonstrated that homocysteine (Hcy) suppresses endothelial cell (EC) proliferation, migration, and post-injury EC repair, but the molecular mechanism underlying Hcy-induced EC injury is unclear. In this study, we identified a novel gene, Carom, which mediates Hcy-induced suppression of EC migration and angiogenesis. We identified FCH and double SH3 domains 2 (FCHSD2), a novel gene, as an Hcy-responsive gene through Differential Display in Hcy (50µM)-treated human umbilical vein endothelial cells (HUVEC). FCHSD2 was initially named as Carom, based on the identification of this molecule as an interacting protein of calcium/calmodulin-dependent serine protein kinase (CASK) and membrane associated guanylate kinase, WW and PDZ domain containing 1 (MAGI1). In this thesis, we describe this gene as Carom. Carom belongs to the Fes/CIP4 homology and Bin/amphiphysin/Rvs (F-BAR) protein family, which is a group of multivalent adaptors linking plasma membrane and cytoskeleton, involved in endocytosis and cell migration. However, Carom's function is poorly characterized. Based on the findings that CASK and MAGI1 inhibit cell migration and growth, and the role of F-BAR proteins in cell migration, we hypothesize that Hcy up-regulates Carom to inhibit EC growth and/or migration, finally leading to CVD. We confirmed the significant induction of Carom mRNA expression in Hcy-treated HUVECs or human aortic endothelial cells (HAEC) by Northern blot and Real-time PCR. In addition, we found that Carom protein expressions were significantly increased both in Hcy-treated HAECs and lung ECs isolated from HHcy mice by Western blot using our homemade rabbit antibody against Carom. These data indicate that Hcy increases endothelial expression of Carom both in vitro and in vivo. Furthermore, in order to characterize Carom function in EC, we generated recombinant adenovirus Adv-Carom to transduce Carom for gain-of-function study and Adv-Carom-shRNA to express Carom shRNA for loss-of-function study. We found that neither adenovirus-transduced Carom expression nor adenoviral Carom shRNA had any impact on HUVEC proliferation by using [3H]-thymidine incorporation. Interestingly, we demonstrated that Adv-Carom inhibited HAEC migration, while Hcy-induced HEAC migration inhibition could be rescued by Adv-Carom-shRNA. These data suggest that Carom may inhibit angiogenesis via a cell proliferation-independent mechanism. Furthermore, we found that Hcy significantly increased the intracellular level of S-adenosyl homocysteine (SAH) but not S-adenosyl methionine (SAM), and decreased the SAM/SAH ratio, an indicator of cellular methylation, in HAECs, by using High-performance liquid chromatography/electrospray tandem mass spectrometry (HPLC-MS) to measure SAH and SAM levels. Meanwhile, Carom protein expression was significantly induced by azacytidine (AZC), a DNA methyltransferse inhibitor, in a dose-dependent manner in HAECs. Based on these…

Advisors/Committee Members: Wang, Hong, Yang, Xiao-Feng;, Wang, Hong, Yang, Xiao-Feng, Ashby, Barrie, Merali, Salim, Xiao, Weidong, Susztak, Katalin;.

Subjects/Keywords: Molecular biology; Biology;

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

APA (6th Edition):

Xiong, X. (2014). Carom, a novel gene, is up-regulated by homocysteine through DNA hypomethylation to inhibit endothelial cell migration and angiogenesis. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,276456

Chicago Manual of Style (16th Edition):

Xiong, Xinyu. “Carom, a novel gene, is up-regulated by homocysteine through DNA hypomethylation to inhibit endothelial cell migration and angiogenesis.” 2014. Doctoral Dissertation, Temple University. Accessed April 14, 2021. http://digital.library.temple.edu/u?/p245801coll10,276456.

MLA Handbook (7th Edition):

Xiong, Xinyu. “Carom, a novel gene, is up-regulated by homocysteine through DNA hypomethylation to inhibit endothelial cell migration and angiogenesis.” 2014. Web. 14 Apr 2021.

Vancouver:

Xiong X. Carom, a novel gene, is up-regulated by homocysteine through DNA hypomethylation to inhibit endothelial cell migration and angiogenesis. [Internet] [Doctoral dissertation]. Temple University; 2014. [cited 2021 Apr 14]. Available from: http://digital.library.temple.edu/u?/p245801coll10,276456.

Council of Science Editors:

Xiong X. Carom, a novel gene, is up-regulated by homocysteine through DNA hypomethylation to inhibit endothelial cell migration and angiogenesis. [Doctoral Dissertation]. Temple University; 2014. Available from: http://digital.library.temple.edu/u?/p245801coll10,276456

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