内皮素-1诱导大鼠肾小管上皮细胞转分化的可能机制

肾脏病与透析肾移植杂志 ›› 2013, Vol. 22 ›› Issue (2): 130-133.

内皮素-1诱导大鼠肾小管上皮细胞转分化的可能机制

出版日期:2013-04-28 发布日期:2013-04-29

Endothelin-1 induced tubular epithelial-mesenchymal transition in rat

Online:2013-04-28 Published:2013-04-29

摘要/Abstract

摘要：

【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-钙粘蛋白（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-SMA mRNA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。

关键词: 【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

Abstract:

【Abstract】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, α-smooth muscle actin (α-SMA), p38mitogen-activated protein kinase (p38MAPK) and phosphorylated-p38MAPK (p-p38MAPK). RT-PCR was used to detect the mRNA expressions of E-cadherin and α-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 α-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 antagonists BQ123 (P<0.05). The p38MAPK specific inhibitor SB203580 also significantly inhibited the changes of morpholog of the cells, E-cadherin, α-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). Conlusions: ET-1 can down-regulate the expressions of E-cadherin and up-regulate the expressions of α-SMA by activating the p38MAPK pathway in renal tubular epithelial cells, which then induces tubular epithelial cell transition.

Key words: 【Key Words】Endothelin-1;Renal tubular epithelial cell, Epithelial-mesenchymal transition, Renal interstitial fibrosi

唐琳，张娜娜，李慧，等. 内皮素-1诱导大鼠肾小管上皮细胞转分化的可能机制[J]. 肾脏病与透析肾移植杂志, 2013, 22(2): 130-133.

TANG Lin , ZHANG Na-na, LI Hui,et al. Endothelin-1 induced tubular epithelial-mesenchymal transition in rat[J]. Chinese Journal of Nephrology, Dialysis & Transplantation, 2013, 22(2): 130-133.

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