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

105 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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10.1016/j.bbrc.2003.08.102

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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 = "Elsevier B.V.",

number = "4",

}

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

UR - https://www.scopus.com/pages/publications/0141453279

U2 - 10.1016/j.bbrc.2003.08.102

DO - 10.1016/j.bbrc.2003.08.102

M3 - Article

C2 - 13679067

AN - SCOPUS:0141453279

SN - 0006-291X

VL - 309

SP - 961

EP - 966

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

Bibliographical note

Keywords

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