Review
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World J Biol Chem. May 26, 2014; 5(2): 180-203
Published online May 26, 2014. doi: 10.4331/wjbc.v5.i2.180
Endoglin in liver fibrogenesis: Bridging basic science and clinical practice
Steffen K Meurer, Muhammad Alsamman, David Scholten, Ralf Weiskirchen
Steffen K Meurer, Ralf Weiskirchen, Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, D-52074 Aachen, Germany
Muhammad Alsamman, David Scholten, Department of Internal Medicine III, RWTH University Hospital Aachen, D-52074 Aachen, Germany
Author contributions: All authors contributed to the manuscript.
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
Correspondence to: Ralf Weiskirchen, Professor, Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstr 30, D-52074 Aachen, Germany. rweiskirchen@ukaachen.de
Telephone: +49-241-8088683 Fax: +49-241-8082512
Received: November 20, 2013
Revised: December 29, 2013
Accepted: January 17, 2014
Published online: May 26, 2014
Processing time: 202 Days and 12.7 Hours
Abstract

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 membrane-bound 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.

Keywords: Telangiectasia; Signalling; Transforming growth factor-β; Disease; Bleeding disorders

Core tip: Endoglin is an accessory receptor for transforming growth factor-β impacting various aspects of its signaling and biological functions. Endoglin mutations are inherited as autosomal dominant disorders and may cause severe defects in different organs, including brain, lung and liver. In the present review, we will highlight the pathogenesis of several of these disorders and give an overview about the important role of endoglin dysfunction in the pathology of liver fibrosis.