Endoglin in liver fibrogenesis: Bridging basic science and clinical practice

作     者：Steffen K Meurer Muhammad Alsamman David Scholten Ralf Weiskirchen 

作者机构：Institute of Clinical Chemistry and Pathobiochemistry RWTH University Hospital Aachen D-52074 Aachen Germany Department of Internal Medicine Ⅲ RWTH University Hospital Aachen D-52074 Aachen Germany 

出 版 物：《World Journal of Biological Chemistry》 (世界生物化学杂志（英文版）（电子版）)

年 卷 期：2014年第5卷第2期

页      面：180-203页

学科分类：1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：Supported by Deutsche Forschungsgemeinschaft SFB/TRR57,P13 and P26 A grant from the Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University IZKF Aachen,Project E6-11,to Weiskirchen R 

主　　题：Telangiectasia Signalling Transforming growth factor-β Disease Bleeding disorders 

摘      要：Endoglin, also known as cluster of differentiation CD105, was originally identified 25 years ago as a novel marker of endothelial cells. Later it was shown that endoglin is also expressed in pro-fibrogenic cells including mesangial cells, cardiac and scleroderma fibroblasts, and hepatic stellate cells. It is an integral membranebound disulfide-linked 180 kDa homodimeric receptor that acts as a transforming growth factor-β(TGF-β) auxiliary co-receptor. In humans, several hundreds of mutations of the endoglin gene are known that give rise to an autosomal dominant bleeding disorder that is characterized by localized angiodysplasia and arteriovenous malformation. This disease is termed hereditary hemorrhagic telangiectasia type Ⅰ and induces various vascular lesions, mainly on the face, lips, hands and gastrointestinal mucosa. Two variants of endoglin(i.e., S- and L-endoglin) are formed by alternative splicing that distinguishes from each other in the length of their cytoplasmic tails. Moreover, a soluble form of endoglin, i.e.,sol-Eng, is shedded by the matrix metalloprotease-14 that cleaves within the extracellular juxtamembrane region. Endoglin interacts with the TGF-β signaling receptors and influences Smad-dependent and-independent effects. Recent work has demonstrated that endoglin is a crucial mediator during liver fibrogenesis that critically controls the activity of the different Smad branches. In the present review, we summarize the present knowledge of endoglin expression and function, its involvement in fibrogenic Smad signaling, current models to investigate endoglin function, and the diagnostic value of endoglin in liver disease.