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[PPARγ up-regulates TGFβ/smad signal pathway repressor c-Ski.] [Article in Chinese]

LI Gong-Bo, LI Jun, ZENG Yi-Jun, ZHONG Dan, WU Geng-Ze, FU Xiao-Hong, HE Feng-Tian, DAI Shuang-Shuang^*

Department of Biochemistry and Molecular Biology； Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China

Abstract

TGFβ/smad pathway is recognized as an important signal pathway to promote the pathogenesis of atherosclerosis (AS). Peroxisome proliferator-activated receptor γ (PPARγ) activation is considered to be important in modulating AS. Herein, we investigated the regulation of PPARγ on c-Ski, the repressor of TGFβ/smad pathway, in rat AS model and cultured vascular smooth muscle cells (VSMCs). c-Ski mRNA and protein expression were detected by real-time PCR and Western blot, respectively, in vivo and in vitro with treatment of PPARγ agonist rosiglitazone and antagonist GW9662. The proliferation and collagen secretion of VSMCs after c-Ski transfection were investigated. The underlying mechanism was further investigated by online program NUBIScan and luciferase reporter gene analysis. Results showed that both mRNA and protein expressions of c-Ski in the AS lesions was down-regulated in vivo, while in cultured VSMCs, c-Ski transfection significantly suppressed the proliferation and collagen secretion of rat VSMCs. Rosiglitazone significantly up-regulated mRNA and protein levels of c-Ski in VSMCs, which could be blocked by GW9662. Online NUBIScan analysis suggested possible PPARγ binding sites in the promoter region of c-Ski. In addition, luciferase activity of c-Ski reporter gene was also increased obviously in the presence of rosiglitazone. These results indicate that c-Ski is one of the newly found target genes of PPARγ and thus involved in the anti-AS effect of PPARγ.

Key words: peroxisome proliferator-activated receptor γ; c-Ski; atherosclerosis; Vascular smooth muscle cell

Received: 2010-10-29　　Accepted: 2010-12-15

Corresponding author: 戴双双　　E-mail: tmmubiodss@yahoo.com.cn

Citing This Article：

LI Gong-Bo, LI Jun, ZENG Yi-Jun, ZHONG Dan, WU Geng-Ze, FU Xiao-Hong, HE Feng-Tian, DAI Shuang-Shuang. [PPARγ up-regulates TGFβ/smad signal pathway repressor c-Ski.] [Article in Chinese]. Acta Physiol Sin 2011; 63 (1): 62-68 (in Chinese with English abstract).