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Acta Physiologica Sinica ; (6): 62-68, 2011.
Artigo em Chinês | WPRIM | ID: wpr-337703

RESUMO

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.


Assuntos
Animais , Masculino , Ratos , Anilidas , Farmacologia , Aterosclerose , Células Cultivadas , Músculo Liso Vascular , Biologia Celular , Miócitos de Músculo Liso , Metabolismo , PPAR gama , Fisiologia , Proteínas Proto-Oncogênicas , Genética , Metabolismo , RNA Mensageiro , Genética , Metabolismo , Ratos Wistar , Proteínas Repressoras , Genética , Metabolismo , Transdução de Sinais , Proteínas Smad , Metabolismo , Tiazolidinedionas , Farmacologia , Fator de Crescimento Transformador beta , Metabolismo , Regulação para Cima
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