Danielle Alberti Memorial Centre for Diabetes Complications, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
Cells Tissues Organs. 2011;193(1-2):74-84. doi: 10.1159/000320359. Epub 2010 Nov 2.
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)-β(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.
肾内肾素-血管紧张素系统（RAS）的激活和随后血管紧张素 II（Ang II）的产生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 Ang II 的作用不仅限于血液动力学作用。Ang II 也是诱导生长因子（包括转化生长因子-β(1)和结缔组织生长因子）的管状肥大的重要刺激物。在本文中，我们探讨了 Ang II 的直接促纤维化作用及其在诱导肾小管上皮细胞向间充质转化（EMT，也称为 2 型 EMT）中的作用，这是肾纤维化的已知介质。越来越多的证据表明，Ang II 能够通过 TGF 依赖性和 TGF 非依赖性作用在体外和体内诱导 EMT。此外，RAS 阻断在多种因果不同形式的肾脏疾病中具有协同的肾脏保护作用。人们希望在 RAS 阻断的情况下针对 ACE 逃逸的靶向组合最终能够实现长期疗效，这是人们长期以来所期望的。
