title: TWEAK and LTβ Signaling during Chronic Liver Disease.
abstract: Chronic liver diseases (CLD) such as hepatitis B and C virus infection, alcoholic liver disease, and non-alcoholic steatohepatitis are associated with hepatocellular necrosis, continual inflammation, and hepatic fibrosis. The induced microenvironment triggers the activation of liver-resident progenitor cells (LPCs) while hepatocyte replication is inhibited. In the early injury stages, LPCs regenerate the liver by proliferation, migration to sites of injury, and differentiation into functional biliary epithelial cells or hepatocytes. However, when this process becomes dysregulated, wound healing can progress to pathological fibrosis, cirrhosis, and eventually hepatocellular carcinoma. The other key mediators in the pathogenesis of progressive CLD are fibrosis-driving, activated hepatic stellate cells (HSCs) that usually proliferate in very close spatial association with LPCs. Recent studies from our group and others have suggested the potential for cytokine and chemokine cross-talk between LPCs and HSCs, which is mainly driven by the tumor necrosis factor (TNF) family members, TNF-like weak inducer of apoptosis (TWEAK) and lymphotoxin-β, potentially dictating the pathological outcomes of chronic liver injury.
authors.affiliation: School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University , Bentley, WA , Australia.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Dwyer
authors.affiliation: School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University , Bentley, WA , Australia ; School of Medicine and Pharmacology, University of Western Australia , Fremantle, WA , Australia ; Department of Gastroenterology, Fremantle Hospital , Fremantle, WA , Australia ; Institute for Immunology and Infectious Diseases, Murdoch University , Murdoch, WA , Australia.
authors.forename: John K
authors.initials: JK
authors.lastname: Olynyk
authors.affiliation: Faculty of Medicine and Biomedical Sciences, The University of Queensland , Brisbane, QLD , Australia ; QIMR Berghofer Medical Research Institute , Brisbane, QLD , Australia.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Ramm
authors.affiliation: School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University , Bentley, WA , Australia ; School of Medicine and Pharmacology, University of Western Australia , Fremantle, WA , Australia.
authors.forename: Janina E E
authors.initials: JE
authors.lastname: Tirnitz-Parker
keywords: LTβ; NFκB; TWEAK; cancer; fibrosis; hepatic stellate cells; liver progenitor cells; regeneration