姜黄素通过调节小凹蛋白1改善高糖透析液诱导的腹膜间皮细胞转分化  

Curcumin Inhibits Epithelial-to-mesenchymal Transition of Peritoneal Mesothelial Cells Via Regulating Caveolin-1

作　　者：陈祥军 孙丽娜 黄峰[2] CHEN Xiangjun;SUN Lina;HUANG Feng(Linyi Traditional Chinese Medicine Hospital,Linyi,276000)

机构地区：[1]临沂市中医医院,临沂276000 [2]临沂市人民医院,临沂276000

出　　处：《中国中西医结合肾病杂志》2022年第7期575-580,共6页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：山东省自然科学基金青年项目(No.ZR2020QH063);山东省中医药科技发展计划项目(No.2017-467)。

摘　　要：目的:通过观察姜黄素对腹膜间皮细胞小凹蛋白1(caveolin-1,cav-1)表达及腹膜间皮细胞间充质转分化(epithelial-to-mesenchymal transition,EMT)的影响,探讨姜黄素防治腹膜透析相关腹膜纤维化的作用及机制。方法:体外培养人腹膜间皮细胞株(HMrSV5细胞),将细胞随机分为:对照组(control组)、模型组(PDS组)、干预组(PDS+姜黄素组),采用Western-blot、Real time-qPCR、免疫荧光法检测α平滑肌肌动蛋白(α-SMA)、E钙黏蛋白(E-cadherin)、转化生长因子β_(1)(TGF-β_(1))、及cav-1的表达。然后通过基因siRNA基因沉默的方法构建cav-1低表达的人腹膜间皮细胞系,采用Western-blot、Real time-qPCR法检测α-SMA、E-cadherin、TGF-β_(1)及p-smad2的表达。结果:高糖腹膜透析液诱导可导致α-SMA及TGF-β_(1)表达的上调同时导致E-cadherin、cav-1表达的下调,姜黄素可部分逆转高糖腹膜透析液的这种作用。cav-1 siRNA+PDS组较高糖透析液组明显加重了间皮细胞转分化的程度,且可上调TGF-β_(1)及p-smad2的表达。结论:高糖腹膜透析液可诱导腹膜间皮细胞转分化。姜黄素可通过调节cav-1/TGF-β信号通路抑制高糖腹膜透析液诱导的腹膜间皮细胞转分化。Objective:To explore the effect and mechanisms of curcumin on the expression of caveolin-1(cav-1)and epithelial to mesenchymal transition(EMT)in peritoneal mesothelial cells from peritoneal dialysis patients.Methods:Human peritoneal mesothelial cells(HMrSV5)were cultured for experiments in vitro.We cultured HMrSV5 with glucose-based peritoneal dialysis solutions(PDS)to induce EMT.HMrSV5 cells were randomly divided into three groups:control group,PDS group,and PDS+curcuin group.Real time qPCR and western blot were used to detect the changes in the expression of EMT markers(E-cadherin,α-SMA).We further detected the production of TGF-β,cav-1 and the expression of p-smad2/smad.We also explored whether cav-1 inhibition by siRNA aggravated EMT in human peritoneal mesothelial cells.Results:The expressions of E-cadherin,α-SMA,cav-1,p-smad in HMrSV5 cells were detected by westem blot.The expressions of TGF-β was detected by ELISA.Glucose-based PDS decreased expression of epithelial markers(E-cadherin),and increased expression of mesenchymal markers(α-SMA),a characteristic of EMT.Glucose-based PDS downregulated the cav-1 protein expression,increased TGF-β production,activated TGF-β/Smad2 signalling in HMrSV5.Curcumin inhibited TGF-β/Smad signaling transmission by up-regulating cav-1,thereby inhibiting EMT.Conclusion:The cav-1/TGFβ signaling pathway may thus be involved in the process of EMT of peritoneum,and the up-regulation of cav-1 by curcumin can significantly attenuate PDS induced EMT.

关 键 词：腹膜间皮细胞 姜黄素 细胞转分化 小凹蛋白 

分 类 号：R285[医药卫生—中药学]