miR-182-5p通过PTEN-AKT信号通路调节肾纤维化  

miR-182-5p regulates renal interstitial fibrosis through PTEN-AKT signaling pathway

作　　者：张璐[1] 程晖[1] 田茂青 宋远 张丽丽[1] ZHANG Lu;CHENG Hui;TIAN Maoqing;SONG Yuan;ZHANG Lili(Dept.of Nephrology,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院肾内科,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2021年第6期907-912,共6页Medical Journal of Wuhan University

基　　金：国家自然科学基金资助项目(编号:81800614)。

摘　　要：目的:研究miR-182-5p在肾脏纤维化中的作用,探讨miR-182-5p在肾纤维化发生发展中的可能机制。方法:检索GEO数据库,分析miR-182-5p在单侧输尿管梗阻(UUO)小鼠肾脏中的表达;收集肾组织标本,检测miR-182-5p的表达;构建UUO肾纤维化小鼠模型,分别予以miR-182-5p抑制剂或阴性对照miRNA处理。Masson染色、天狼星红染色评价各组小鼠肾间质纤维化改变;Western印迹法检测肾组织fibronectin、Ⅰ型胶原纤维(collagen-Ⅰ)、α-平滑肌肌动蛋白(α-SMA)、磷酸酶张力蛋白同源物(PTEN)、蛋白激酶B(AKT)及磷酸化AKT的表达水平。结果:miR-182-5p在慢性肾脏病及单侧输尿管梗阻小鼠肾组织中的表达均显著升高(P<0.05)。肾脏Masson及天狼星红染色结果显示,UUO组较sham组小鼠肾纤维化程度明显加重;与miRNA阴性对照+UUO组比较,miR-182-5p抑制剂+UUO组肾间质胶原纤维显著减少,纤维化程度显著减轻(P<0.05)。Western印迹结果显示,与miRNA阴性对照+UUO相比较,miR-182-5p抑制剂可拮抗UUO模型肾组织fibronectin、collagen-Ⅰ、α-SMA的表达上调,诱导PTEN的表达,减少AKT的过度磷酸化(均P<0.05)。结论:miR-182-5p在肾纤维化的进程中起重要作用,其作用机制与PTEN-AKT信号通路有关。Objective:To investigate the role and underlying mechanism of miR-182-5 p on renal interstitial fibrosis.Methods:The GEO database was implied to analyze the expression of miR-182-5 p in mice model of unilateral ureteral obstruction(UUO).The abundance of miR-182-5 p in kidney of chronic kidney disease was analyzed by qRT-PCR.UUO mouse model was established and injected with miR-182-5 p inhibitor and negative control reagent through caudal vein,respectively.Renal fibrosis was evaluated by Masson staining and picro-sirius red staining.The expression levels of fibronectin,collagen-Ⅰ,α-smooth muscle actin(SMA),phosphatase tensin homolog(PTEN),protein kinase B(AKT),and p-AKT were analyzed by Western Blotting in four groups.Results:The expression of miR-182-5 p was significantly increased in the kidneys of chronic kidney disease and UUO mice(P<0.05).A large amount of collagen deposition was observed in the renal interstitial area in UUO mice as compared with that in sham group.After the treatment with miR-182-5 p inhibitor,the renal fibrosis was decreased as compared with that in UUO mice model(P<0.05).Moreover,compared with that in UUO group,miR-182-5 p inhibitor treatment significantly down-regulated the expression of fibronectin,collagen-Ⅰ,and α-SMA,up-regulated the expression of PTEN,and decreased the phosphorylation of AKT(all P<0.05).Conclusion:miR-182-5 p plays a critical role in renal fibrosis through regulation of PTEN-AKT signaling pathway.

关 键 词：miR-182-5p 输尿管梗阻 纤维化 肾间质 PTEN 

分 类 号：R692.5[医药卫生—泌尿科学]