罗格列酮对多囊肾囊肿衬里上皮细胞中β-catenin表达的影响  

Effects of Rosigliazone on β-catenin Expression in Cystic-lining Epithelial Cells of ADPKD

作　　者：刘沫言[1] 刘春艳[1] 付莉莉[1] 王清佾[1] 梅长林[1] 

机构地区：[1]第二军医大学附属长征医院,解放军肾脏病研究所,上海200003

出　　处：《中国中西医结合肾病杂志》2009年第6期477-480,I0001,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：上海市重点学科建设基金资助项目(No.B902)

摘　　要：目的:分析多囊肾组织和正常肾组织中β-catenin表达分布差异,并观察罗格列酮对人多囊肾囊肿衬里上皮细胞(WT9～12)中β-catenin蛋白水平的干预作用。方法:免疫组织化学方法检测人多囊肾组织及多囊肾动物模型PKDV/V小鼠肾组织与其相应正常肾组织中β-catenin表达分布差异;MTT法检测不同浓度罗格列酮对WT9～12增殖抑制情况;RT-PCR技术检测罗格列酮干预后β-catenin mRNA水平;Western blot技术检测β-catenin的表达。结果:正常肾小管上皮细胞β-catenin主要在胞膜分布,胞核及胞浆少见;囊肿衬里上皮细胞中β-catenin蛋白表达水平明显增加,且存在核转位;PKDV/V小鼠囊肿衬里上皮细胞胞核β-catenin呈强阳性分布。罗格列酮对WT9～12有增殖抑制作用,其作用72h后,对β-catenin mRNA水平无影响,但可明显下调β-catenin蛋白水平,且加入PPAR-γ阻断剂后不能阻断罗格列酮的下调作用。结论:多囊肾组织中存在Wnt/β-catenin通路异常,罗格列酮可抑制多囊肾囊肿衬里上皮细胞增殖,其作用机制可能与下调β-catenin表达从而抑制Wnt/β-catenin通路有关,并且这种下调作用通过非PPAR-γ依赖性途径实现。Objective：Analyze on expression of β- catenin in kidney of patients and PKDV/V mouse with autosomal dominant polycystic kidney disease, and investigate the effects of rosiglitazone on β- catenin in WT9- 12 cells. Methyls： Abnormal distribution of β- catenin in ADPKD patients and PKDV/V mouse were detected by immunohistochemical method. The inhibition of WT9- 12 cells, which were treated with rosiglitazone, proliferation was detected by MTT. Effects of rosiglitazone on level of β- catenin mRNA was identified by semi - quantitative RT - PCR, andthe protein levels of β- catenin were detected by western blot. Results：The location of β- catenin was predominantly in membrane and few in cytoplasm and nucleus in normal renal tubule epithelia Cell, but the expressions of β- catenin were significant enhanced not only in cytoplasm but also in nucleus in polycystic kidney cyst - lining epithelial cells. These changes were also found in the PKDV/V mouse tissues. Rosiglitazone can inhibit cell proliferation, but has no effect on the expression of β-catenin mRNA. It can negative regulate the protein level of β-catenin, and the PPAR - γ blocker can not prevent the down- regulation effects of Rosiglitazone. Conclusion：Rosiglitazone can inhibit WT9- 12 proliferation by down regulating the protein level of β-catenin and the location of the abnormal Wnt/β- catenin pathway supports the view that dysregulation of the Wnt/β- catenin signaling may be involved in this pathogenesis. And the regulation effects is not dependent on the PPAR -γ pathway.

关 键 词：罗格列酮 WNT/Β-CATENIN PPAR-Γ 多囊肾囊肿衬里上皮细胞 增殖 

分 类 号：R692.1[医药卫生—泌尿科学]