Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
Nephrology (Carlton). 2010 Aug;15(5):507-12. doi: 10.1111/j.1440-1797.2010.01319.x.
Diabetic nephropathy (DN) is the most common cause of chronic kidney failure and end-stage renal disease in the Western world. Studies from diabetic animal models and clinical trials have shown that inhibition of the renin-angiotensin system delays the progression of advanced DN. However, a recent large-scale clinical trial has revealed that inhibition of renin-angiotensin system in early phases of DN does not slow the decline of renal function or the development of morphological lesions, suggesting that different mechanism(s) may be involved in the different stages of DN. The role of epithelial-mesenchymal transition in renal fibrosis has been intensively investigated. Recently, endothelial-mesenchymal transition, or endothelial-myofibroblast transition (EndoMT) has emerged as another mechanism involved in both developmental and pathological processes. The essential role of EndoMT in cardiac development has been thoroughly studied. EndoMT also exists and contributes to the development and progression of cardiac fibrosis, lung fibrosis, liver fibrosis and corneal fibrosis. EndoMT is a specific form of epithelial-mesenchymal transition. During EndoMT, endothelial cells lose endothelial markers and obtain mesenchymal markers. Recent evidence from our laboratory and others suggests that EndoMT plays an important role in the development of renal fibrosis in several pathological settings, including experimental DN. This review considers the evidence supporting the occurrence of EndoMT in normal development and in pathology, as well as the latest findings suggesting EndoMT contributes to fibrosis in DN. Whether experimental findings of EndoMT will be reproduced in human studies remains to be determined.
糖尿病肾病（DN）是西方世界最常见的慢性肾衰竭和终末期肾病的病因。来自糖尿病动物模型和临床试验的研究表明，肾素-血管紧张素系统的抑制可延缓晚期 DN 的进展。然而，最近一项大规模临床试验表明，DN 早期抑制肾素-血管紧张素系统并不能减缓肾功能下降或形态损伤的发展，这表明不同的机制可能参与了 DN 的不同阶段。上皮-间充质转化在肾纤维化中的作用已得到深入研究。最近，内皮-间充质转化或内皮-肌成纤维细胞转化（EndoMT）已成为另一种涉及发育和病理过程的机制。EndoMT 在心脏发育中的重要作用已得到深入研究。EndoMT 也存在于并促进心脏纤维化、肺纤维化、肝纤维化和角膜纤维化的发生和发展。EndoMT 是上皮-间充质转化的一种特殊形式。在 EndoMT 过程中，内皮细胞失去内皮标志物并获得间充质标志物。我们实验室和其他实验室的最新证据表明，EndoMT 在几种病理情况下，包括实验性 DN 中，对肾纤维化的发展起着重要作用。这篇综述考虑了支持 EndoMT 在正常发育和病理学中发生的证据，以及最新发现表明 EndoMT 有助于 DN 中的纤维化。EndoMT 的实验发现是否会在人类研究中重现还有待确定。
