白藜芦醇对高糖刺激下人肾小管上皮细胞发生EMT的作用  

Role of Resveratrol on High Glucose-induced Epithelial to Mesenchymal Transition of Human Renal Proximal Tubular Epithelial Cells

作　　者：吴海江[1] 邓新娜[2] 史永红[1] 郭庆军[1] 李宏博[1] 彭金凯 庞磊[3] 崔桂鹏 段惠军[1] 

机构地区：[1]河北医科大学病理学教研室河北省肾脏病重点实验室,石家庄050017 [2]河北省人民医院肿瘤四科,石家庄050051 [3]河北医科大学基础医学院,石家庄050017

出　　处：《中国细胞生物学学报》2015年第11期1522-1527,共6页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:81370825);河北省卫生计生委医学科学研究课题计划项目(批准号:ZL20140063);2014年河北省高等学校科学技术研究项目(批准号:Z2014053);河北医科大学大学生创新性实验计划项目(批准号:USIP201564A)资助的课题~~

摘　　要：该文研究了白藜芦醇及其下游信号分子沉默信息调节因子1(silent information regulator 1,SIRT1)对高糖培养条件下人肾小管上皮细胞(HK-2)转化的作用和机制。体外常规培养HK-2细胞,采用Western blot检测平滑肌肌动蛋白(α-SMA)、E-钙黏着蛋白(E-cadherin)及信号蛋白SIRT1、过氧化物酶体增殖物激活受体γ协同刺激因子-1α(peroxisome proliferator-activated receptor gamma coactivator-1α,PGC-1α)的蛋白表达,采用细胞免疫荧光对SIRT1的表达进行检测。与高糖刺激0 h组相比,高糖刺激12,24,48 h均导致HK-2细胞SIRT1蛋白明显减少,且随时间呈下降趋势;低糖培养细胞0,12,24,48 h的SIRT1蛋白表达没有明显差异。白藜芦醇明显提高高糖培养条件下HK-2细胞的SIRT1表达,而SIRT1特异性抑制剂EX527能够减弱白藜芦醇的作用。进一步的研究表明,白藜芦醇能够明显增加HK-2细胞中E-钙黏着蛋白的表达,抑制高糖导致的α-SMA表达升高,而EX527对高糖诱导的HK-2细胞转分化没有显著影响。此外,研究发现,白藜芦醇能够明显增加高糖刺激下HK-2细胞PGC-1α蛋白表达。该研究结果提示,白藜芦醇可能通过SIRT1和PGC-1α信号通路抑制了高糖诱导的HK-2细胞转化过程。We investigated the role of resveratrol and SIRT1 signaling pathway on epithelial to mesenchymal transition of human renal proximal tubular epithelial cells （HK-2） cultured with high glucose. HK-2 cells were cultured in vitro. The protein levels of α-SMA, E-cadherin, SIRT1 and PGC-1αwere determined by Western blot. The expression level of SIRT1 was also examined by immunofluorescence assay. Compared with 0 h, the exposure of HK-2 cells to high concentration of glucose resulted in decreased protein levels of SIRT 1 in a time-dependent manner. But HK-2 cells incubated with low concentrations of glucose for various periods didn＇t show a time-dependent decrease in SIRT1 expression. Resveratrol treatment resulted in increased protein level of SIRT1. This effect was markedly diminished by the addition of EX527, an inhibitor of SIRT1. Furthermore, resveratrol treatment also resulted in increased protein level of E-cadherin, along with a down-regulation of α-SMA, although EX527 alone had no effect on high glucose-induced EMT of HK-2 cells. In addition, resveratrol treatment also prevented the decrease of PGC-1 α in HK-2 cells cultured with high glucose. Taken together, these data demonstrated that resveratrol could prevent high glucose-induced EMT of human renal proximal tubular epithelial cells via activation of SIRT1 and PGC- 1 α signaling pathway.

关 键 词：白藜芦醇 肾小管上皮细胞 HK-2细胞 上皮细胞-间充质细胞转化 SIRT1 PGC-1Α 

分 类 号：R285[医药卫生—中药学]