Interaction of thrombospondin1 and CD36 contributes to obesity-associated podocytopathy

Wenpeng Cui, Hasiyeti Maimaitiyiming, Qi Zhou, Heather Norman, Changcheng Zhou, Shuxia Wang

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish
Pages (from-to)1323-1333
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1852
Issue number7
DOIs
StatePublished - Jul 1 2015

Bibliographical note

Funding Information:
This study was supported in part by the U.S. Department of Veterans Affairs Merit Review Award (to S. Wang), the National Institutes of Health (NIH) Grant R01 DK081555 and DK098176 (to S. Wang), NIH Training Grant DK07778 (to H. Norman), and a COBRE grant P20GM103527-06 .

Publisher Copyright:
© 2015 Elsevier B.V.

Keywords

  • CD36
  • Free fatty acid
  • Obesity
  • Podocyte apoptosis
  • TSP1

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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