Angiotensin II and Its Role in Tubular Epithelial to Mesenchymal Transition Associated with Chronic Kidney Disease
Angiotensin II and Its Role in Tubular Epithelial to Mesenchymal Transition Associated with Chronic Kidney Disease
复制标题
DOI：
10.1159/000320359
复制
发表时间：
2011-01-01
影响因子：
2.7
通讯作者：
Thomas, M. C.
中科院分区：
文献类型：
--
作者：
Burns, W. C.;Thomas, M. C.
肾内肾素-血管紧张素系统（RAS）的激活和随后产生的血管紧张素II（Ang II）是健康和疾病中血液动力学变化的重要介质。然而，局部产生的血管紧张素II的影响不仅限于血液动力学作用。血管紧张素II也是一个重要的刺激肾小管肥大的诱导生长因子，包括转化生长因子（TGF）-β（1）和结缔组织生长因子。在这篇文章中，我们探讨了血管紧张素II的直接促纤维化作用及其在诱导肾小管上皮细胞间质转化（EMT，也称为2型EMT），一种已知的肾纤维化介质中的作用。有越来越多的证据表明，血管紧张素II能够诱导EMT的TGF依赖性和TGF非依赖性的行动，在体外和体内。此外，阻断RAS对多种病因不同的肾脏疾病具有协同肾保护作用。有希望的是，在RAS阻断的情况下，靶向组合抵消血管紧张素转换酶逃逸将最终实现长期预期的疗效。版权所有（C）2010 S. Karger AG，巴塞尔
Activation of the intra-renal renin-angiotensin system (RAS) and the subsequent generation of angiotensin II (Ang II) are important mediators of haemodynamic changes in both health and disease. However, the effects of locally produced Ang II are not limited to haemodynamic actions. Ang II is also an important stimulus for tubular hypertrophy with the induction of growth factors, including transforming growth factor (TGF)-beta(1) and connective tissue growth factor. In this article, we explore the direct pro-fibrotic effects of Ang II and its role in inducing tubular epithelial to mesenchymal transition (EMT, also known as type 2 EMT), a known mediator of renal fibrogenesis. There is accumulating evidence that Ang II is able to induce EMT by both TGF-dependent and TGF-independent actions, both in vitro and in vivo. Moreover, blockade of the RAS has synergistic renoprotective effects across a number of causally different forms of renal disease. There is hope that targeted combinations to offset angiotensin-converting enzyme escape in the setting of RAS blockade will eventually achieve the long-term efficacy that has been expected for so long. Copyright (C) 2010 S. Karger AG, Basel