Angiotensin-(1-7) attenuates high glucose-induced proximal tubular epithelial-to-mesenchymal transition via inhibiting ERK1/2 and p38 phosphorylation
Angiotensin-(1-7) attenuates high glucose-induced proximal tubular epithelial-to-mesenchymal transition via inhibiting ERK1/2 and p38 phosphorylation
复制标题
Angiotensin-(1-7) 通过抑制 ERK1/2 和 p38 磷酸化来减弱高葡萄糖诱导的近端肾小管上皮间质转化。
DOI：
10.1016/j.lfs.2011.12.015
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发表时间：
2012-03-10
期刊：
影响因子：
6.1
通讯作者：
Lu, Limin
中科院分区：
文献类型：
--
作者：
Zhou, Li;Xue, Hong;Lu, Limin
目的：肾脏是肾素-血管紧张素系统中血管紧张素II和血管紧张素-(1-7)[Ang-(1-7)]的重要靶点。然而，Ang-(1-7)的肾功能尚不清楚。本研究旨在探讨Ang-(1-7)对高糖诱导的肾上皮细胞向间充质转化（EMT）的影响。主要方法：采用培养的肾上皮细胞（NRK-52E）进行实验。荧光免疫细胞化学观察α -平滑肌肌动蛋白（α - sma）的变化。采用Real-time PCR和Western blot检测mRNA和蛋白水平。采用酶联免疫吸附法测定培养基中转化生长因子- β 1 （tgf - β 1）的浓度。主要发现：高糖诱导血管紧张素转换酶相关羧肽酶（ACE2）和Mas mRNA水平降低。同时，高糖诱导α - sma和vimentin升高，E-cadherin降低，tgf - β 1和纤维连接蛋白分泌升高。Ang-(1-7)部分逆转了高糖诱导的α - sma、vimentin、E-cadherin、tgf - β 1和纤维连接蛋白的变化。高糖刺激了ERK、p38和JNK的磷酸化，Ang-(1-7)逆转了ERK和p38的变化，但对JNK的磷酸化没有作用。意义：高糖状态下ACE2-Ang-(1-7)- mas轴的抑制和不足参与EMT。补充Ang-(1-7)可减弱高糖诱导的EMT。ERK和p38细胞内信号通路介导Ang-(1-7)对EMT的影响，而不是JNK。(C) 2012爱思唯尔公司版权所有。
Aims: The kidney is an important target for both Angiotensin II and angiotensin-(1-7) [Ang-(1-7)] in the renin-angiotensin system. However, the renal function of Ang-(1-7) remains unclear. This study is aimed at investigating the effect of Ang-(1-7) on high glucose-induced epithelial to mesenchymal transition (EMT) in cultured renal epithelial cells.Main methods: Cultured renal epithelial (NRK-52E) cell line was used in the experiment. Fluorescence immunocytochemistry was performed to observe alpha-smooth muscle actin (alpha-SMA). Real-time PCR and Western blot were used to determine mRNA and protein levels. Enzyme-linked immunosorbent assay was used to measure the concentration of transforming growth factor-beta 1 (TGF-beta 1) in the culture media.Key findings: High glucose-induced decreased in both angiotensin-converting enzyme-related carboxypeptidase (ACE2) and Mas mRNA levels. Meanwhile, high glucose induced increases in alpha-SMA and vimentin, decreases in E-cadherin, elevations in TGF-beta 1 and fibronectin secretions. Ang-(1-7) partially reversed high glucose-induced changes in alpha-SMA, vimentin, E-cadherin, TGF-beta 1 and fibronectin. High glucose stimulated ERK, p38 and JNK phosphorylation and Ang-(1-7) reversed the changes in ERK and p38 but not JNK phosphorylation.Significance: Inhibition and insufficiency in ACE2-Ang-(1-7)-Mas axis under high glucose condition participate EMT. Supplementation of Ang-(1-7) attenuates high glucose-induced EMT. ERK and p38 intracellular signaling pathways, not JNK, mediate the effect of Ang-(1-7) on EMT. (C) 2012 Elsevier Inc. All rights reserved.