title: TGF-β in progression of liver disease.
abstract: Transforming growth factor-β (TGF-β) is a central regulator in chronic liver disease contributing to all stages of disease progression from initial liver injury through inflammation and fibrosis to cirrhosis and hepatocellular carcinoma. Liver-damage-induced levels of active TGF-β enhance hepatocyte destruction and mediate hepatic stellate cell and fibroblast activation resulting in a wound-healing response, including myofibroblast generation and extracellular matrix deposition. Being recognised as a major profibrogenic cytokine, the targeting of the TGF-β signalling pathway has been explored with respect to the inhibition of liver disease progression. Whereas interference with TGF-β signalling in various short-term animal models has provided promising results, liver disease progression in humans is a process of decades with different phases in which TGF-β or its targeting might have both beneficial and adverse outcomes. Based on recent literature, we summarise the cell-type-directed double-edged role of TGF-β in various liver disease stages. We emphasise that, in order to achieve therapeutic effects, we need to target TGF-β signalling in the right cell type at the right time.
authors: Molecular Hepatology-Alcohol Associated Diseases II Medical Clinic Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. steven.dooley@medma.uni-heidelberg.de
authors: Steven
authors: S
authors: Dooley
authors: Peter
authors: P
authors: ten Dijke
mesh_terms: D000818:Animals; D002908:Chronic Disease; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D006801:Humans; D008107:Liver Diseases / Q000473:pathology* / Q000503:physiopathology; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta