1. PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-γ AGONISTS ATTENUATE ANGIOTENSIN II-INDUCED COLLAGEN TYPE I EXPRESSION IN ADVENTITIAL FIBROBLASTS.
- Author
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Jia Zhang, Ning-Yuan Fang, Ping-Jin Gao, Ling-Yun Wu, Wei-Qing Han, Shu-Jie Guo, Wei-Li Shen, and Ding-Liang Zhu
- Subjects
ANGIOTENSIN II ,PROSTAGLANDINS ,FIBROBLASTS ,OXIDATIVE stress ,REACTIVE oxygen species ,TRANSCRIPTION factors - Abstract
1. 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 J2 (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. [ABSTRACT FROM AUTHOR]- Published
- 2008
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