PPAR-¦Ã activation by rosiglitazone suppresses angiotensin II-mediated proliferation and phenotypictransition in cardiac fibroblasts via inhibition of activation of activator protein 1
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- 作者：Xiaoyang Hou ; Ying Zhang ; Ying H. Shen ; Tongbao Liu ; Shangming Song ; Lianqun Cui ; Peili Bu
- 关键词：Differentiation ; Peroxisome proliferator-activated receptor-¦Ã ; Cardiac fibroblast ; Cyclin D1 ; Activator protein-1
- 刊名：European Journal of Pharmacology
- 出版年：2013
- 出版时间：5 September, 2013
- 年：2013
- 卷：715
- 期：1-3
- 页码：196-203
- 全文大小：1877 K
文摘
Cardiac fibroblasts play an important role in myocardial remodeling by proliferating, differentiating, and secreting extracellular matrix proteins. Peroxisome proliferator-activated receptor-¦Ã (PPAR-¦Ã) ligands have been reported to have a number of cardioprotective properties. However, the mechanism underlying this protective effect has not yet been elucidated. The purpose of the present study was to investigate the effect of rosiglitazone on angiotensin II-induced cardiac fibroblast proliferation and differentiation. Cardiac fibroblasts were stimulated with angiotensin II (10-7 M) in the presence or absence of rosiglitazone (10-5 nM). Pretreatment of cardiac fibroblasts with rosiglitazone significantly inhibited angiotensin II-induced cardiac fibroblast proliferation and profibrotic phenotypes differentiation and, thus, reduced the overall production of collagen components. PPAR-¦Ã antagonist GW9662 significantly inhibited these effects of rosiglitazone, suggesting that these effects of rosiglitazone were PPAR-¦Ã-dependent. To investigate the mechanisms involved, we found that PPAR-¦Ã activation by rosiglitazone inhibited the formation of c-fos/c-jun heterodimers and expression of activator protein 1 induced by ANG II and thus inhibited transcription of the downstream genes involved in CFs proliferation and differentiation. Our data suggests PPAR-¦Ã activation could have an anti-fibrotic effect through limiting cardiac fibroblast proliferation and differentiation, which are the critical steps in the pathogenesis of cardiac fibrosis.