SIP1在TGF—β1诱导的人腹膜间皮细胞转分化的作用  

Roles of SIP1 in TGF- 1 Induced Epithelial-mesenchymal Transition of Human Peritoneal Mesothelial Ceils

作　　者：周循[1] 凌光辉[1] 孙林[1] 刘伏友[1] 

机构地区：[1]中南大学湘雅二医院肾内科,中南大学肾脏病研究所,湖南长沙410011

出　　处：《医学临床研究》2010年第7期1185-1189,共5页Journal of Clinical Research

基　　金：国家自然科学基金（编号30871169）

摘　　要：【目的】阐明Smad作用蛋白1（Smad interacting proteinl，SIP1）与转化生长因子－β1（transforming growth factor－β1，TGF-β1）诱导的人腹膜间皮细胞（human peritoneal mesothelial cells）转分化（epithelial—mesenchymal transition，EMT）的关系，探讨TGF－β1可能通过调控SIP1引起腹膜间皮细胞EMT的机制。【方法】培养的人腹膜间皮细胞株（HMrSV5）随机分为对照组（TGF-β1刺激Oh）和TGF－β1刺激组，通过western blot及realtime PCR检测细胞中E－钙粘素（E－eadherin）、紧密连接蛋白（claudinl）、波形蛋白（vimentin）及纤维连接蛋白（fibronectin，FN）在不同时间点（12h，24h，48h，72h）的表达；并通过western blot及realtime PCR检测相应时间点细胞中SIP1的表达。【结果】5ng／ml TGF－β1刺激后，HMrsV5细胞E-cadherin、claudinl蛋白及mRNA表达水平呈时间依赖性降低（P〈0．01）；vimentin、FN蛋白及mRNA表达水平呈时间依赖性升高（P〈0．01）；SIP1蛋白及mRNA表达水平呈时间依赖性上调（P〈0．01）。【结论】TGF-β1可能通过上调HMrSV5细胞SIP1表达诱导HMrSV5细胞EMT及细胞外基质（extracellular matrix，ECM）沉积，将为进一步研究腹膜纤维化的分子机制提供新的靶点。[Objective]To investigate the relationship between Smad interacting proteinl （SIP1） and trans- forming growth faetor-βl （TGF-β1） induced epithelial mesenchymal transition （EMT） in human peritoneal mesothelial cells（HPMC）, and explore the mechanism of TGF-β1 induced EMT through SIP1. [Methods] HMrSV5 cell lines were exposed to 5ng/ml TGF-β1. The expressions of E-cadherin, claudinl, vimentin and fibronectin（FN） were examined by western blot and real-time PCR at the time stimulated for Oh, 12h, 24h, 48h and 72h. Meanwhile, the expression of SIP1 was also examined by western blot and real-time PCR. [Results]Stimulation of HMrSV5 cells with TGF-β1 5ng/ml resulted in a significant decrease of E-cadherin and claudinl, and an increase of vimentin and FN in time-dependent manner （ P 〈 0. 01）. Stimulation of HMrSV5 cells with TGF-β1 resulted in a significant increase of SIP1 in time-dependent manner（ P 〈0. 01）. [Conclusion]TGF-β1 induced EMT may be modulated via up-regulation of SIP1. It provides a new target for exploration of the mechanism of peritoneal fibrosis.

关 键 词：腹膜/细胞学 间质细胞 转化生长因子Β 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学]