高糖诱导肾小管上皮细胞发生上皮-间质转化过程中Snail 1对IGF-1表达的影响  

The effect of Snail 1 on the expression of Insulin-like growth factor-1 in high glucose-induced epithelial-mesenchymal transition in renal tubular epithelial cells

作　　者：潘祉谕 俞佳丽[1] 孙翼[1] 董蓉[2] 达静静[2] 左丽[1] 查艳[1] PAN Zhi -yu YU Jia - li SUN Yi DONG Rong DA Jing -ring ZUO Li ZHA Yan(Department of lmmunology, Guizhou Medical University, Guiyang 550004, Guizhou, Chin)

机构地区：[1]贵州医科大学免疫学教研室,贵州贵阳550004 [2]贵州省人民医院肾内科,贵州贵阳550002

出　　处：《广东医学》2017年第15期2265-2270,共6页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(编号:81200539);贵州省科技厅-贵州省人民医院联合基金项目(黔科合LH字[2014]7002号,黔科合LH字[2015]7155号,黔科合LH字[2015]7154号,黔科合LH字[2016]7169号);贵州省卫生计生委科学技术基金项目(编号:gzwkj2014-1-046)

摘　　要：目的研究锌指转录因子1(Snail 1)对高糖诱导的发生上皮-间质转化(epithelial to mesenchymal transition,EMT)的大鼠肾小管上皮细胞(NRK-52E)中胰岛素样生长因子-1(insulin-like growth factor 1,IGF-1)表达的影响,探讨糖尿病肾脏病发生机制及Snail 1与自分泌IGF-1的相关性。方法大鼠近端肾小管上皮细胞系(NRK-52E),分组如下:对照组、高糖组、高糖+NT组、高糖+siRNA组。分别于培养48 h、72 h收获细胞。用免疫荧光、原位杂交等方法检测细胞Snail 1、IGF-1、E-钙黏蛋白(E-cadherin)和纤维连接蛋白(fibronectin,FN)mRNA及蛋白的表达。结果与对照组相比,高糖组细胞IGF-1、Snail 1和FN的mRNA及蛋白表达明显增加,差异有统计学意义(P<0.01)。E-cadherin的mRNA及蛋白表达明显减少,差异有统计学意义(P<0.01);与高糖组相比,高糖+siRNA组细胞IGF-1、Snail 1和FN的mRNA及蛋白表达明显减少,差异有统计学意义(P<0.01),E-cadherin的mRNA及蛋白表达明显增加,差异有统计学意义(P<0.01);与高糖组相比,高糖+NT组IGF-1、Snail 1、E-cadherin和FN的mRNA及蛋白表达,差异无统计学意义(P>0.05)。Spearman's相关性分析显示,NRK-52E细胞中Snail 1与IGF-1蛋白的表达呈正相关(r=0.936,P<0.05)。结论高糖诱导肾小管上皮细胞发生EMT的过程中Snail 1可能通过调节IGF-1促进糖尿病肾脏病肾脏纤维化。Objective To investigate the effect of Snail 1 on the expression of insulin - like growth factor - 1 （IGF- 1 ） in high glucose- induced epithelial- mesenchymal transition （EMT） in NRK- 52E cells, and the roles of Snail 1 and autocrine IGF - 1 in diabetic kidney disease （DKD）. Methods The NRK - 52E cells were divided into four groups, control group, high glucose group, high glucose ＋ NT group and high glucose ＋ siRNA group. The expression of Snail 1, IGF - 1, E - cadherin and FN in the mRNA and protein levels were assessed with in situ hybridization and immunofluorescence, after 48 hours and 72 hours culturing. Results Compared with control group, the mRNA and protein levels of IGF - 1, Snail 1 and FN of high glucose group were significantly elevated （ all P 〈 0. 01 ）, as E - cadherin were reduced （ P 〈 0. 01 ）. The reduction in the mRNA and the protein levels of IGF - 1, Snail 1 and FN in high glucose ＋ siRNA group were significant compared with high glucose group （all P 〈0. 01 ）, as significant elevation in E -cadherin was revealed （P 〈 0. 01 ）. the expression of IGF - 1, Snail 1, E - cadherin and FN of high glucose ＋ NT group had no signifi- cant change compared with high glucose group （all P 〉 0. 05 ）. Spearman＇s correlation analysis showed that the expression of Snail 1 protein was significantly positively correlated with that of IGF - 1 （ r = 0. 936, P 〈 0. 01 ）. Conclusion During the process of high glucose - induced EMT, Snail 1 may promote DKD renal fibrosis by regulating the expression of IGF - 1.

关 键 词：糖尿病肾脏病 肾纤维化 上皮-间质转化 锌指转录因子1 胰岛素样生长因子-1 

分 类 号：R322.61[医药卫生—人体解剖和组织胚胎学]