title: [PPARγ up-regulates TGFβ/smad signal pathway repressor c-Ski].
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Gong-bo
authors.initials: GB
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Yi-jun
authors.initials: YJ
authors.lastname: Zeng
authors.forename: Dan
authors.initials: D
authors.lastname: Zhong
authors.forename: Geng-ze
authors.initials: GZ
authors.lastname: Wu
authors.forename: Xiao-hong
authors.initials: XH
authors.lastname: Fu
authors.forename: Feng-tian
authors.initials: FT
authors.lastname: He
authors.forename: Shuang-shuang
authors.initials: SS
authors.lastname: Dai
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology; D002478:Cells, Cultured; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D047495:PPAR gamma; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C525545:Ski protein, rat; D051785:Smad Proteins; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D000077154:Rosiglitazone