Upregulation of type I collagen by TGF-β in mesangial cells is blocked by PPARγ activation

Feng Zheng, Alessia Fornoni, Sharon J. Elliot, Youfei Guan, Matthew D. Breyer, Liliane J. Striker, Gary E. Striker

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

We found that peroxisome proliferator-activated receptor-γ (PPARγ) mRNA was reduced by 77% in glomeruli of diabetic mice. Because mesangial cells play an important role in diabetic nephropathy, we examined regulation of type I collagen expression by PPARγ and transforming growth factor-β1 (TGF-β1) in mouse mesangial cells in the presence of 6 and 25 mM glucose. Mesangial cells contained functionally active PPARγ. Exposure to 25 mM glucose resulted in reduced PPARγ expression and transcriptional activity, accompanied by increased type I collagen expression. Restoration of PPARγ activity to normal levels in cells cultured in 25 mM glucose, by transfection with a PPARγ expression construct and treatment with the PPARγ agonist troglitazone, returned type I collagen levels toward normal values. Activation of PPARγ by troglitazone also decreased type I collagen mRNA and blocked TGF-β1-mediated upregulation of type I collagen mRNA and protein. Moreover, PPARγ activation suppressed basal and activated TGF-β1 responses in mesangial cells. This action was blocked by transfection of cells with a dominant-negative PPARγ construct. In summary, PPARγ suppresses the increased type I collagen mRNA and protein expression mediated by TGF-β1 in mesangial cells.

Original languageEnglish (US)
Pages (from-to)F639-F648
JournalAmerican Journal of Physiology - Renal Physiology
Volume282
Issue number4 51-4
DOIs
StatePublished - 2002

Keywords

  • Diabetic nephropathy
  • Peroxisome proliferator-activated receptor-γ
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology

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