PPARγ up-regulates TGFβ/smad signal pathway repressor c-Ski.
- Author:
Gong-bo LI
1
;
Jun LI
;
Yi-jun ZENG
;
Dan ZHONG
;
Geng-ze WU
;
Xiao-hong FU
;
Feng-tian HE
;
Shuang-shuang DAI
Author Information
1. Department of Biochemistry and Molecular Biology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
- Publication Type:Journal Article
- MeSH:
Anilides;
pharmacology;
Animals;
Atherosclerosis;
physiopathology;
Cells, Cultured;
Male;
Muscle, Smooth, Vascular;
cytology;
Myocytes, Smooth Muscle;
metabolism;
PPAR gamma;
agonists;
antagonists & inhibitors;
physiology;
Proto-Oncogene Proteins;
genetics;
metabolism;
RNA, Messenger;
genetics;
metabolism;
Rats;
Rats, Wistar;
Repressor Proteins;
genetics;
metabolism;
Signal Transduction;
Smad Proteins;
metabolism;
Thiazolidinediones;
pharmacology;
Transforming Growth Factor beta;
metabolism;
Up-Regulation
- From:
Acta Physiologica Sinica
2011;63(1):62-68
- CountryChina
- Language:Chinese
-
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.
