The role of ADAM17 during liver damage
Author:
Al-Salihi Mazin12, Bornikoel Anna1, Zhuang Yuan1, Stachura Pawel1, Scheller Jürgen3, Lang Karl S.4, Lang Philipp A.1ORCID
Affiliation:
1. Department of Molecular Medicine II , Medical Faculty, Heinrich Heine University , Universitätsstr. 1 , D-40225 Düsseldorf , Germany 2. School of Medicine , University of Central Lancashire , Preston , PR1 2HE , UK 3. Department of Biochemistry and Molecular Biology II , Medical Faculty , Universitätsstr. 1 , D-40225 Düsseldorf , Germany 4. Institute of Immunology , Medical Faculty, University of Duisburg-Essen , Hufelandstr. 55 , D-45147 Essen , Germany
Abstract
Abstract
A disintegrin and metalloprotease (ADAM) 17 is a membrane bound protease, involved in the cleavage and thus regulation of various membrane proteins, which are critical during liver injury. Among ADAM17 substrates are tumor necrosis factor α (TNFα), tumor necrosis factor receptor 1 and 2 (TNFR1, TNFR2), the epidermal growth factor receptor (EGFR) ligands amphiregulin (AR) and heparin-binding-EGF-like growth factor (HB-EGF), the interleukin-6 receptor (IL-6R) and the receptor for a hepatocyte growth factor (HGF), c-Met. TNFα and its binding receptors can promote liver injury by inducing apoptosis and necroptosis in liver cells. Consistently, hepatocyte specific deletion of ADAM17 resulted in increased liver cell damage following CD95 stimulation. IL-6 trans-signaling is critical for liver regeneration and can alleviate liver damage. EGFR ligands can prevent liver damage and deletion of amphiregulin and HB-EGF can result in increased hepatocyte death and reduced proliferation. All of which indicates that ADAM17 has a central role in liver injury and recovery from it. Furthermore, inactive rhomboid proteins (iRhom) are involved in the trafficking and maturation of ADAM17 and have been linked to liver damage. Taken together, ADAM17 can contribute in a complex way to liver damage and injury.
Publisher
Walter de Gruyter GmbH
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
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