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, YuSeun Kim, Dong Cheol Han, Soo Tack Uh, Choon Sik Park, Hi Bahl Lee

Research output: Contribution to journalArticle

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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 H 2 O 2 stimulates PAI-1 expression and suppresses plasmin activity and that N-acetylcysteine effectively reverses TGF-β1- and H 2 O 2 -induced changes in PAI-1 expression and plasmin activity. Basal as well as TGF-β1- and H 2 O 2 -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

Fingerprint

Mesangial Cells
Plasminogen Activator Inhibitor 1
Transforming Growth Factors
Reactive Oxygen Species
Up-Regulation
Fibrinolysin
Fibrosis
Gene encoding
Extracellular Matrix Proteins
Acetylcysteine
Genetic Promoter Regions
Oxidation-Reduction
Transcription Factors
Binding Sites
Tissue
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Jiang, Zongpei ; Seo, Ji Yeon ; Ha, Hunjoo ; Lee, Eun Ah ; Kim, YuSeun ; Han, Dong Cheol ; Uh, Soo Tack ; Park, Choon Sik ; Lee, Hi Bahl. / Reactive oxygen species mediate TGF-β1-induced plasminogen activator inhibitor-1 upregulation in mesangial cells. In: Biochemical and Biophysical Research Communications. 2003 ; Vol. 309, No. 4. pp. 961-966.
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Reactive oxygen species mediate TGF-β1-induced plasminogen activator inhibitor-1 upregulation in mesangial cells. / Jiang, Zongpei; Seo, Ji Yeon; Ha, Hunjoo; Lee, Eun Ah; Kim, YuSeun; Han, Dong Cheol; Uh, Soo Tack; Park, Choon Sik; Lee, Hi Bahl.

In: Biochemical and Biophysical Research Communications, Vol. 309, No. 4, 03.10.2003, p. 961-966.

Research output: Contribution to journalArticle

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AU - Jiang, Zongpei

AU - Seo, Ji Yeon

AU - Ha, Hunjoo

AU - Lee, Eun Ah

AU - Kim, YuSeun

AU - Han, Dong Cheol

AU - Uh, Soo Tack

AU - Park, Choon Sik

AU - Lee, Hi Bahl

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