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Full-Text Articles in Medicine and Health Sciences
Signalling Via The Osteopontin And High Mobility Group Box-1 Axis Drives The Fibrogenic Response To Liver Injury, Elena Arriazu, Xiaodong Ge, Tung-Ming Leung, Fernando Magdaleno, Aritz Lopategi, Yongke Lu, Naoto Kitamura, Raquel Urtasun, Neil Theise, Daniel J. Antoine, Natalia Nieto
Signalling Via The Osteopontin And High Mobility Group Box-1 Axis Drives The Fibrogenic Response To Liver Injury, Elena Arriazu, Xiaodong Ge, Tung-Ming Leung, Fernando Magdaleno, Aritz Lopategi, Yongke Lu, Naoto Kitamura, Raquel Urtasun, Neil Theise, Daniel J. Antoine, Natalia Nieto
Pharmacology, Physiology and Toxicology
Objective: Liver fibrosis is associated with significant collagen-I deposition largely produced by activated hepatic stellate cells (HSCs); yet, the link between hepatocyte damage and the HSC profibrogenic response remains unclear. Here we show significant induction of osteopontin (OPN) and high-mobility group box-1 (HMGB1) in liver fibrosis. Since OPN was identified as upstream of HMGB1, we hypothesised that OPN could participate in the pathogenesis of liver fibrosis by increasing HMGB1 to upregulate collagen-I expression. Design and results: Patients with long-term hepatitis C virus (HCV) progressing in disease stage displayed enhanced hepatic OPN and HMGB1 immunostaining, which correlated with fibrosis stage, whereas …