title: Endoglin in liver fibrogenesis: Bridging basic science and clinical practice.
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.
authors.affiliation: Steffen K Meurer, Ralf Weiskirchen, Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, D-52074 Aachen, Germany.
authors.forename: Steffen K
authors.initials: SK
authors.lastname: Meurer
authors.affiliation: Steffen K Meurer, Ralf Weiskirchen, Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, D-52074 Aachen, Germany.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Alsamman
authors.affiliation: Steffen K Meurer, Ralf Weiskirchen, Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, D-52074 Aachen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Scholten
authors.affiliation: Steffen K Meurer, Ralf Weiskirchen, Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, D-52074 Aachen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Weiskirchen
keywords: Bleeding disorders; Disease; Signalling; Telangiectasia; Transforming growth factor-β