Thrombospondin 1 deficiency ameliorates the development of adriamycin-induced proteinuric kidney disease

Hasiyeti Maimaitiyiming, Qi Zhou, Shuxia Wang

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish
Article numbere0156144
JournalPLoS ONE
Volume11
Issue number5
DOIs
StatePublished - May 1 2016

Bibliographical note

Publisher Copyright:
© 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.

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Thrombospondin 1 deficiency ameliorates the development of adriamycin-induced proteinuric kidney disease'. Together they form a unique fingerprint.

Cite this