1. Reactive oxygen species mediate TGF-<f>β1</f>-induced plasminogen activator inhibitor-1 upregulation in mesangial cells
- Author
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Jiang, Zongpei, Seo, Ji Yeon, Ha, Hunjoo, Lee, Eun Ah, Kim, Yu Seun, Han, Dong Cheol, Uh, Soo Tack, Park, Choon Sik, and Lee, Hi Bahl
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GROWTH factors , *EXTRACELLULAR matrix , *PLASMINOGEN , *GENE expression - Abstract
Transforming growth factor-
β1 (TGF-β1 ) promotes tissue fibrosis by upregulating genes encoding extracellular matrix proteins and by increasing the synthesis of plasminogen activator inhibitor-1 (PAI-1). TGF-β1 induces cellular reactive oxygen species (ROS) and PAI-1 promoter region has binding sites for redox sensitive transcription factors. We, therefore, hypothesized that TGF-β1 -induced upregulation of PAI-1 is ROS-dependent. Using cultured glomerular mesangial cells, we confirmed that TGF-β1 induces cellular ROS, upregulates PAI-1 mRNA and protein expression, and suppresses plasmin activity. We further demonstrated that H2O2 stimulates PAI-1 expression and suppresses plasmin activity and that N-acetylcysteine effectively reverses TGF-β1 - and H2O2-induced changes in PAI-1 expression and plasmin activity. Basal as well as TGF-β1 - and H2O2-induced PAI-1 expression was upregulated by depletion of intracellular GSH. The present data demonstrate that TGF-β1 -induced PAI-1 in mesangial cells is ROS-dependent and imply that cellular ROS may be potential therapeutic targets in glomerular fibrosis. [Copyright &y& Elsevier]- Published
- 2003
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