Böttinger Erwin P, Bitzer Markus
Unified Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine Bronx, New York 10461, USA.
J Am Soc Nephrol. 2002 Oct;13(10):2600-10. doi: 10.1097/01.asn.0000033611.79556.ae.
Since discovery over a decade ago of a role for the cytokine TGF-beta as key mediator of glomerular and tubulointerstitial pathobiology in chronic kidney diseases, studies of TGF-beta signaling in the kidney have focused on the molecular biology of fibrogenesis. In recent years, glomerular and tubular epithelial cell apoptosis and cellular transdifferentiation have been proposed as putative primary pathomechanisms that may underlie progression of renal disease. This review describes evidence in support of nonlinear models and functional roles of TGF-beta signaling in mediating apoptosis and epithelial-to-mesenchymal transdifferentiation (EMT) in chronic progressive renal disease. Emphasis is placed on cell context-dependent models of TGF-beta signaling providing a conceptual framework to consolidate seemingly distinct pathomechanisms of progression of glomerular and tubulointerstitial disease.
自从十多年前发现细胞因子转化生长因子-β（TGF-β）作为慢性肾脏病肾小球和肾小管间质病理生物学的关键介质以来，肾脏中TGF-β信号传导的研究一直集中在纤维生成的分子生物学上。近年来，肾小球和肾小管上皮细胞凋亡以及细胞转分化被认为是可能构成肾脏疾病进展基础的假定主要发病机制。这篇综述描述了支持TGF-β信号传导在慢性进行性肾脏疾病中介导细胞凋亡和上皮-间充质转化（EMT）的非线性模型及功能作用的证据。重点是TGF-β信号传导的细胞背景依赖性模型，该模型提供了一个概念框架，以整合肾小球和肾小管间质疾病进展中看似不同的发病机制。
