Reactive oxygen species mediate TGF-β1-induced plasminogen activator inhibitor-1 upregulation in mesangial cells

Zongpei Jiang, Ji Yeon Seo, Hunjoo Ha, Eun Ah Lee, Yu Seun Kim, Dong Cheol Han, Soo Tack Uh, Choon Sik Park, Hi Bahl Lee

Research output: Contribution to journalArticle

93 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)961-966
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume309
Issue number4
DOIs
Publication statusPublished - 2003 Oct 3

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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