PPARγ up-regulates TGFβ/smad signal pathway repressor c-Ski / 生理学报
Acta Physiologica Sinica
;
(6): 62-68, 2011.
Artigo
em Chinês
| WPRIM
| ID: wpr-337703
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Fisiologia
/
Proteínas Repressoras
/
RNA Mensageiro
/
Transdução de Sinais
/
Regulação para Cima
/
Células Cultivadas
/
Fator de Crescimento Transformador beta
/
Proteínas Proto-Oncogênicas
/
Ratos Wistar
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Chinês
Revista:
Acta Physiologica Sinica
Ano de publicação:
2011
Tipo de documento:
Artigo
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