[HTML][HTML] TGF-β in progression of liver disease

S Dooley, P Ten Dijke - Cell and tissue research, 2012 - Springer
S Dooley, P Ten Dijke
Cell and tissue research, 2012Springer
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 …
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.
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