Counteraction between angiotensin II and angiotensin-(1-7) via activating angiotensin type I and Mas receptor on rat renal mesangial cells
Counteraction between angiotensin II and angiotensin-(1-7) via activating angiotensin type I and Mas receptor on rat renal mesangial cells
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血管紧张素II和血管紧张素-(1-7)通过激活大鼠肾系膜细胞血管紧张素I型和Mas受体的拮抗作用
DOI：
10.1016/j.regpep.2012.04.002
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发表时间：
2012-08-20
影响因子：
--
通讯作者：
Lu, Limin
中科院分区：
文献类型：
--
作者：
Xue, Hong;Zhou, Li;Lu, Limin
在更新的概念中，肾素-血管紧张素系统（RAS）包含血管紧张素转换酶（ACE）-血管紧张素（Ang）II-血管紧张素1型受体（All）轴和血管紧张素转换酶相关羧肽酶（ACE 2）-Ang-（1-7）-Mas轴。前一个轴已被充分证明通过激活A11受体执行血管收缩、增殖和促炎功能，而后来新鉴定的轴被认为抵消了前一个的作用。本研究旨在观察血管紧张素-（1-7）和血管紧张素Ⅱ（Ang Ⅱ）对体外培养的大鼠肾小球系膜细胞（MCs）的相互作用。RT-PCR、Western blot、免疫荧光染色和共聚焦显微镜观察结果表明，大鼠肾脏MC中A11和Mas受体共分布。Ang-（1-7）对培养的MC中的Ang II表现出类似的作用，其刺激磷酸化的细胞外信号调节激酶（ERK）1/2磷酸化并转化生长因子β 1合成、细胞增殖和细胞外基质合成。Ang-（1-7）和Ang Ⅱ共同处理细胞，Ang-（1-7）以浓度依赖性方式抵消Ang Ⅱ诱导的效应，但不能改变内皮素-1诱导的变化。Ang-（1-7）的作用可被Mas受体拮抗剂A-779阻断，但不能被A11受体拮抗剂氯沙坦或AT 2受体拮抗剂PD 123319阻断。提示Ang-（1-7）和Ang Ⅱ在大鼠肾MC上通过激活其特异性受体而发生特异性相互作用。Mas和All受体。(C)2012爱思唯尔有限公司版权所有。
In the updated concept of renin-angiotensin system (RAS), it contains the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-angtiogensin type 1 receptor (All) axis and the angiotensin-converting enzyme-related carboxypeptidase (ACE2)-Ang-(1-7)-Mas axis. The former axis has been well demonstrated performing the vasoconstrictive, proliferative and pro-inflammatory functions by activation of All receptors, while the later new identified axis is considered counterbalancing the effects of the former. The present study is aimed at observing the interaction between Ang-(1-7) and Ang II on cultured rat renal mesangial cells (MCs). RT-PCR, Western blot and immunofluorescent staining and confocal microscopy results showed that both All and Mas receptor were co-distributed in rat renal MCs. Ang-(1-7) showed similar effects on Ang II in cultured MCs that stimulated phosphorylated extracellular signal-regulated kinase (ERK)1/2 phosphorylation and transforms growth factor-beta 1 synthesis, and cell proliferation and extracellular matrix synthesis. Co-treatment of the cell with Ang-(1-7) and Ang II, Ang-(1-7) counteracted AngII-induced effects in a concentration dependent manner, but failed to alter the changes induced by endothelin-1. The stimulating effect of Ang II was mediated by All receptor while all the effects of Ang-(1-7) were blocked by Mas receptor antagonist A-779, but not by All receptor antagonist losartan or AT2 receptor antagonist PD123319. These results suggest that Ang-(1-7) and Ang II specifically interact with each other on rat renal MCs via activation of their specific receptors. Mas and All receptor respectively. (C) 2012 Elsevier B.V. All rights reserved.