内皮素-1诱导大鼠肾小管上皮细胞转分化的可能机制  

Endothelin-1 induced tubular epithelial-mesenchymal transition in rat

作　　者：唐琳[1,2] 张娜娜[1,2] 李慧[1,2] 陈慧娟[1,2] 刘章锁[1,2] 

机构地区：[1]郑州大学第一附属医院肾内科 [2]郑州大学肾脏病研究所,郑州450052

出　　处：《肾脏病与透析肾移植杂志》2013年第2期130-133,174,共5页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：河南省高等学校青年骨干教师资助计划(2010GGJS-004)

摘　　要：目的:探讨内皮素-1(ET-1)是否可诱导大鼠肾小管上皮细胞转分化(TEMT)及可能的分子机制。方法:体外培养大鼠肾小管上皮细胞(NRK52E)并进行分组;倒置显微镜观察细胞的形态变化;Western印迹法检测细胞E钙黏蛋白(E-cadherin)、α平滑肌肌动蛋白(α-SMA)、p38丝裂原活化蛋白激酶(p38MAPK)及磷酸化-p38MAPK(p-p38MAPK)蛋白的表达;逆转录-聚合酶链反应(RT-PCR)法检测细胞E-cadherin及α-SMAmRNA的表达。结果:ET-1可诱导细胞由鹅卵石样变为梭形,下调E-cadherin表达,上调α-SMA、p38MAPK及p-p38MAPK表达,增强p38MAPK活性(P<0.05),而内皮素A受体拮抗剂BQ123能明显抑制这些变化(P<0.05)。p38MAPK特异性抑制剂SB203580可抑制ET-1诱导的细胞梭形性变,ET-1诱导的E-cadherin、α-SMA及p-p38MAPK表达改变及p38MAPK活性改变(P<0.05),但对p38MAPK表达无明显影响(P>0.05)。结论:ET-1可能通过激活肾小管上皮细胞p38MAPK通路,下调E-cadherin的表达,同时上调α-SMA的表达,从而诱导肾小管上皮细胞转分化。Objective：To investigate whether endothelin-1 （ET-1） could induce tubular epithelial-mesenchymal transition （TEMT）and the possible molecular mechanisms. Methodology： The rat renal tubular epithelial cells （NRK52E） were cultured in vitro and divided into several groups. The cells morphological changes were observed with inverted microscope. Western blot was used to assess the protein expression levels of E-cadherin, a-smooth muscle actin （a-SMA）, p38mitogen-activated protein kinase （p38MAPK） and phosphorylated-p38MAPK （p-p38MAPK）. RT-PCR was used to detect the mRNA expressions of E-eadhefin and a-SMA. Results ：The cobble-shaped renal tubular epithelial cells were induced to become fusiform by ET-1 which meanwhile down-regulated the expression of E-cadherin, whereas up regulated the expressions of a-SMA, p38MAPK and p-p38MAPK and enhanced the activity of p38MAPK （P 〈 0. 05 ）. All of these changes induced by ET-1 were obviously inhibited by the endothelin A receptor antagonist BQ123 （ P 〈 0. 05 ）. The p38MAPK specific inhibitor SB203580 also significantly inhibited the changes of morpholog of the cells, E-cadherin, ct-SMA and p-p38MAPK expressions and p38MAPK activity induced by ET-1 （ P 〈 0. 05 ）, but had no significant effect on the expression of p38MAPK （P 〉 0.05）. Conclusion： ET-1 can down-regulate the expressions of E-cadherin and up-regulate the expressions of a-SMA by activating the p38MAPK pathway in renal tubular epithelial cells,which then induces tubular epithelial-mesenchymal transition.

关 键 词：内皮素1 肾小管上皮细胞上皮细胞转分化 肾间质纤维化 

分 类 号：R692[医药卫生—泌尿科学]