Abstract
Accumulating evidence suggests that thrombospondin 1 (TSP1) is an important player in diabetic nephropathy. However, the role of TSP1 in podocyte injury and the development of non-diabetic proteinuric kidney disease is largely unknown. In the current study, by using a well-established podocyte injury model (adriamycin-induced nephropathy mouse model), we examined the contribution of TSP1 to the development of proteinuric kidney disease. We found that TSP1 was up-regulated in the glomeruli, notably in podocytes, in adriamycin injected mice before the onset of proteinuria. ADR treatment also stimulated TSP1 expression in cultured human podocytes in vitro. Moreover, increased TSP1 mediated ADR-induced podocyte apoptosis and actin cytoskeleton disorganization. This TSP1’s effect was through a CD36-dependent mechanism and involved in the stimulation of p38MAPK pathway. Importantly, in vivo data demonstrated that TSP1 deficiency protected mice from ADR induced podocyte loss and foot process effacement. ADR induced proteinuria, glomerulosclerosis, renal macrophage infiltration and inflammation was also attenuated in TSP1 deficient mice. Taken together, these studies provide new evidence that TSP1 contributes to the development of non-diabetic proteinuric kidney disease by stimulating podocyte injury and the progression of renal inflammation.
Document Type
Article
Publication Date
5-19-2016
Digital Object Identifier (DOI)
https://doi.org/10.1371/journal.pone.0156144
Funding Information
This study was supported in part by National Institutes of Health (NIH) Grants R01 DK 081555, DK098176 and R03AG047452 (to S. Wang).
Repository Citation
Maimaitiyiming, Hasiyeti; Zhou, Qi; and Wang, Shuxia, "Thrombospondin 1 Deficiency Ameliorates the Development of Adriamycin-Induced Proteinuric Kidney Disease" (2016). Pharmacology and Nutritional Sciences Faculty Publications. 47.
https://uknowledge.uky.edu/pharmacol_facpub/47
Included in
Medical Nutrition Commons, Medical Pharmacology Commons, Pharmacology, Toxicology and Environmental Health Commons
Notes/Citation Information
Published in PLOS ONE, v. 11, no. 5, e0156144, p. 1-15.
© 2016 Maimaitiyiming et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.