title: Interaction of thrombospondin1 and CD36 contributes to obesity-associated podocytopathy.
abstract: Obesity is associated with podocyte injury and the development of proteinuria. Elevated plasma free fatty acid is one of the characteristics of obesity and has been linked to podocyte dysfunction. However, the mechanisms remain unclear. In the current study, we examined the effect of saturated free fatty acid (FFA) on human podocyte apoptosis and function in vitro. The mechanism and its in vivo relevance were also determined. We found that FFA treatment induced human podocyte apoptosis and dysfunction, which was associated with increased expression of a matricellular protein-thrombospondin1 (TSP1). FFA stimulated TSP1 expression in podocytes at the transcriptional levels through activation of MAPK pathway. Addition of purified TSP1 to cell culture media induced podocyte apoptosis and dysfunction. Tis effect is though a TGF-β independent mechanism. Moreover, peptide treatment to block TSP1 binding to its receptor-CD36 attenuated FFA induced podocyte apoptosis, suggesting that TSP1/CD36 interaction mediates FFA-induced podocyte apoptosis. Importantly, using a diet-induced obese mouse model, in vivo data demonstrated that obesity-associated podocyte apoptosis and dysfunction were attenuated in TSP1 deficient mice as well as in CD36 deficient mice. Taken together, these studies provide novel evidence that the interaction of TSP1 with its receptor CD36 contributes to obesity--associated podocytopathy.
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA; Department of Nephrology, Second Hospital of Jilin University, Changchun 130041, China.
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA; Lexington Veterans Affairs Medical Center, Lexington, KY, USA.
authors.forename: Hasiyeti
authors.initials: H
authors.lastname: Maimaitiyiming
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA; Lexington Veterans Affairs Medical Center, Lexington, KY, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA; Lexington Veterans Affairs Medical Center, Lexington, KY, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Norman
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Changcheng
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA; Lexington Veterans Affairs Medical Center, Lexington, KY, USA. Electronic address: swang7@uky.edu.
authors.forename: Shuxia
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005227:Fatty Acids / Q000633:toxicity; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D005227:Fatty Acids; D019700:Thrombospondin 1; C585483:Thbs1 protein, mouse
keywords: CD36; Free fatty acid; Obesity; Podocyte apoptosis; TSP1
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