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PEROXISOME PROLIFERATOR‐ACTIVATED RECEPTOR‐γ AGONISTS ATTENUATE ANGIOTENSIN II‐INDUCED COLLAGEN TYPE I EXPRESSION IN ADVENTITIAL FIBROBLASTS
Author(s) -
Zhang Jia,
Fang NingYuan,
Gao PingJin,
Wu LingYun,
Han WeiQing,
Guo ShuJie,
Shen WeiLi,
Zhu DingLiang
Publication year - 2008
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04748.x
Subject(s) - angiotensin ii , peroxisome proliferator activated receptor , pioglitazone , chemistry , endocrinology , medicine , receptor , oxidative stress , activator (genetics) , electrophoretic mobility shift assay , western blot , fibroblast , intracellular , transcription factor , microbiology and biotechnology , biology , in vitro , biochemistry , gene , type 2 diabetes , diabetes mellitus
SUMMARY1 Angiotensin (Ang) II‐mediated oxidative stress may be important in enhanced adventitial fibroblast collagen formation. The aim of the present study was to test whether PPAR‐γ agonists 15‐deoxy‐Δ 12,14 ‐prostaglandin J 2 (15d‐PGJ2) and pioglitazone could alter AngII‐induced collagen type I formation in vascular adventitial fibroblasts via reactive oxygen species (ROS). 2 Vascular adventitial fibroblasts were isolated from rat thoracic aortas of male Sprague‐Dawley rats and treated with different concentrations of AngII for different periods of time. The expression of collagen type I induced by AngII was examined by western blot. Expression of PPAR‐γ mRNA was examined by reverse transcription–polymerase chain reaction (RT‐PCR). Intracellular ROS generation was measured by flow cytometry. Activation of transcription factors nuclear factor (NF)‐κB and activator protein (AP)‐1 was assessed by an electrophoretic mobility shift assay. 3 Angiotensin II increased expression of collagen type I in a time‐ and dose‐dependent manner in adventitial fibroblasts. In addition, AngII stimulated intracellular generation of ROS in adventitial fibroblasts. Pretreatment of cells with 15d‐PGJ2 and pioglitazone attenuated collagen type I expression and generation of ROS induced by AngII, respectively. Moreover, we observed that N ‐acetylcysteine inhibited collagen type I expression induced by AngII as did the PPAR‐γ agonists. Angiotensin II treatment activated the redox‐sensitive transcription factors NF‐κB and AP‐1, whereas pretreatment with 15d‐PGJ2 and pioglitazone reduced the AngII‐induced DNA‐binding activity of NF‐κB but not AP‐1. 4 Our data demonstrate that the PPAR‐γ agonists 15d‐PGJ2 and pioglitazone attenuate AngII‐mediated collagen type I expression in adventitial fibroblasts, which may be mediated by the modulation of ROS release and the redox‐sensitive transcription factor NF‐κB.