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PPARγ up-regulates TGFβ/smad signal pathway repressor c-Ski
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- Author:
- No author available
- Journal Title:
- ACTA PHYSIOLOGICA SINICA
- Issue:
- 1
- DOI:
- No doi available
- Key Word:
- 氧化物酶体增殖物激活受体γ;c-Ski;动脉粥样硬化;血管平滑肌细胞
Abstract： 本文旨在研究过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)对动脉粥样硬化(atherosclerosis,AS)形成中关键信号通路TGFβ/smad途径的阻遏子c-Ski的调控作用,探讨PPARγ抗AS的分子机制.通过高脂饮食制作大鼠AS模型,检测AS斑块中c-Ski的mRNA及蛋白的表达变化;在体外培养的大鼠血管平滑肌细胞(vascular smoothmuscle cell,VSMC)中转染重组c-Ski质粒,并观察其对VSMC增殖及胶原分泌影响;采用real-time PCR和Western blot检测PPARγ激动剂和拮抗剂对c-Ski表达的调节,进而利用在线程序NUBIScan及荧光素酶报告基因检测明确PPARγ对c-Ski的调控机理.结果显示:AS大鼠动脉斑块中c-Ski mRNA和蛋白表达显著降低;重组c-Ski转染显著抑制大鼠VSMC增殖及胶原分泌;PPARγ激动剂罗格列酮可明显上调大鼠VSMC中c-Ski表达,且这种上调可以被PPARγ拮抗剂GW9662所阻断.生物信息学分析表明c-Ski启动子区有可能的PPARγ结合位点,而罗格列酮也能显著上调转染了c-Ski的报告基因表达.以上结果表明c-Ski具有一定抗AS作用,其可能是PPARγ的又一靶基因,激活PPARγ可上调c-Ski而发挥抗AS作用.
- [1]杨鹏远,芮耀诚,焦亚斌.动脉粥样硬化大鼠实验模型的建立[J].2003,(7).
- [2]Kwak HJ,Go SH,Lim HJ,etc.15d-PGJ2 stimulates HO-1 expression through p38 MAP kinase and Nrf-2 pathway in rat vascular smooth muscle cells.[J].2007,223(1).
- [3]S, Kersten,B, Desvergne,W, Wahli.Roles of PPARs in health and disease.[J].2000,405(6785).
- [4]Mitsuru, Abe,Koji, Hasegawa,Hiromichi, Wada,etc.GATA-6 is involved in PPARgamma-mediated activation of differentiated phenotype in human vascular smooth muscle cells.[J].2003,23(3).
- [5]Mortensen RM,Usher MG,Duan SZ.Peroxisome proliferator-activated receptor-gamma-mediated effects in the vasculature.[J].2008,102(3).
- [6]Gu D,Wang Z,Li P,etc.The essential role for c-Ski in mediating TGF-beta1-induced bi-directional effects on skin fibroblast proliferation through a feedback loop.[J].2008,409(1).
- [7]C J, Hupfeld,R H, Weiss.TZDs inhibit vascular smooth muscle cell growth independently of the cyclin kinase inhibitors p21 and p27.[J].2001,281(2).
- [8]Taub Rebecca,Macias Silva Marina,Leu JuliaI,etc.Up-regulated transcriptional repressors SnoN and Ski bind Smad proteins to antagonize transforming growth factor-beta signals during liver regeneration.[J].2002,277(32).
- [9]Dennis, Bruemmer,Fen, Yin,Joey, Liu,etc.Regulation of the growth arrest and DNA damage-inducible gene 45 (GADD45) by peroxisome proliferator-activated receptor gamma in vascular smooth muscle cells.[J].2003,93(4).
- [10]Turner N,Halka A,Walker MG,etc.The role of transforming growth factor beta(1) in the vascular system.[J].2005,14(1).
- [11]Kintscher U,Kuroki T,Ohba M,etc.Peroxisome proliferator-activated receptor gamma ligands inhibit mitogenic induction of p21(Cip1) by modulating the protein kinase Cdelta pathway in vascular smooth muscle cells.[J].2001,276(50).
- [12]Miyazono K,Yagi K,Kato M,etc.c-Ski inhibits the TGF-beta signaling pathway through stabilization of inactive Smad complexes on Smad-binding elements.[J].2004,23(29).