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

doi:10.1016/j.bbrc.2003.08.102

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

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

100 Scopus citations

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 language	English
Pages (from-to)	961-966
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	309
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2003.08.102
State	Published - 3 Oct 2003

Bibliographical note

Funding Information:
This work was supported by a grant from Korea Research Foundation (KRF 1999-005-F00025).

Keywords

Extracellular matrix
Mesangial expansion
Oxidative stress
Plasmin
Plasminogen activator inhibitor-1
Reactive oxygen species
Renal fibrosis
Signaling pathway
Transforming growth factor-β1

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@article{155cd746e0254bf3b6939d70d59b2979,

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

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.",

keywords = "Extracellular matrix, Mesangial expansion, Oxidative stress, Plasmin, Plasminogen activator inhibitor-1, Reactive oxygen species, Renal fibrosis, Signaling pathway, Transforming growth factor-β1",

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

note = "Funding Information: This work was supported by a grant from Korea Research Foundation (KRF 1999-005-F00025).",

year = "2003",

month = oct,

day = "3",

doi = "10.1016/j.bbrc.2003.08.102",

language = "English",

volume = "309",

pages = "961--966",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

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TY - JOUR

T1 - Reactive oxygen species mediate TGF-β1-induced plasminogen activator inhibitor-1 upregulation in mesangial cells

AU - Jiang, Zongpei

AU - Seo, Ji Yeon

AU - Ha, Hunjoo

AU - Lee, Eun Ah

AU - Kim, Yu Seun

AU - Han, Dong Cheol

AU - Uh, Soo Tack

AU - Park, Choon Sik

AU - Lee, Hi Bahl

N1 - Funding Information: This work was supported by a grant from Korea Research Foundation (KRF 1999-005-F00025).

PY - 2003/10/3

Y1 - 2003/10/3

N2 - 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.

AB - 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.

KW - Extracellular matrix

KW - Mesangial expansion

KW - Oxidative stress

KW - Plasmin

KW - Plasminogen activator inhibitor-1

KW - Reactive oxygen species

KW - Renal fibrosis

KW - Signaling pathway

KW - Transforming growth factor-β1

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

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

Abstract

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Keywords

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