Ski在全反式维甲酸抑制TGF-β1诱导的系膜细胞增殖中的作用  

The Effects of All-Trans Retinoic Acid (ATRA) on the Expression of Ski in Cultured Rat Mesangial Cells Treated by TGF-β_1

作　　者：苏宝凤[1] 王晓花[1] 张莉[1] 于莹[1] 陈晓岚[2] 

机构地区：[1]南京医科大学附属南京医院、南京市第一医院儿科,210006 [2]南通大学附属医院肾内科

出　　处：《天津医药》2013年第4期345-348,共4页Tianjin Medical Journal

基　　金：江苏省自然科学基金(项目编号:BK2008185);南通市社会发展基金(项目编号:S2007027)

摘　　要：目的探讨全反式维甲酸(ATRA)对转化生长因子(TGF)-β1诱导的大鼠系膜细胞增殖及Ski表达的影响。方法不同浓度ATRA预处理大鼠HBZY-1系膜细胞(为各剂量ATRA组)24h后再加TGF-β1(10μg/L)培养24h。CCK-8法检测细胞增殖情况;Real-time PCR法检测SkimRNA的表达;Western blot检测Ski蛋白的表达;激光共聚焦荧光显微镜检测Ski蛋白的亚细胞定位。并与正常对照组及TGF-β1组比较。结果与正常对照组相比,TGF-β1组系膜细胞增殖明显,且Ski mRNA及蛋白表达升高(P<0.05);与TGF-β1组相比,ATRA能够呈剂量依赖性地抑制TGF-β1的促增殖作用,ATRA 10μmol/L组Ski mRNA及蛋白表达量明显增高。ATRA组Ski蛋白主要定位于大鼠系膜细胞核,其细胞核荧光信号强度较TGF-β1组明显增强,细胞浆中荧光信号强度较TGF-β1组减弱。结论 ATRA可通过上调大鼠系膜细胞Ski表达,抑制其向核外转位,从而抑制TGF-β1诱导的系膜细胞增殖。Objective To investigate the effects of all-trans retinoic acid （ATRA） on the expression of Ski in cultured rat mesangial cells treated by transforming growth factor （TGF-β1）. Methods The mesangial cells were pre-treated with different concentrations of ATRA for 24 h, and then stimulated with TGF-β1, （10 μg/L） for 24 h. The cell proliferation was detected by CCK-8 method. The Ski mRNA expression was determined by real time-PCR. The protein expression of Ski was determined by Western blot analyses. The localization of Ski was observed by confocal fluorescence microscopy. Resuits Compared with the control group, TGF-β1 significantly enhanced the proliferation and the expression of Ski mRNA and protein in rat mesangial cells （P 〈 0.05）. ATRA significantly inhibited mesangial cell proliferation induced by TGF-β1, in a dose-dependent manner. In ATRA groups, Ski mRNA and protein were, increased significantly. Additionally, Ski protein was mainly localized in nucleus, and fluorescence intensity was significantly increased in nucleus, while decreased in cytoplasm in ATRA groups. Conclusion ATRA could inhibit TGF-β1 induced mesangial cell proliferation through up-regulating the expression of Ski and inhibiting it translocation from the nucleus to the cytoplasm.

关 键 词：肾小球系膜细胞 细胞系 维甲酸 转化生长因子β1 大鼠 SKI 

分 类 号：R692.602[医药卫生—泌尿科学]