TGF-β in progression of liver disease

Transforming growth factor-beta (TGF-beta) 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-beta 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-beta signalling pathway has been explored with respect to the inhibition of liver disease progression. Whereas interference with TGF-beta 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-beta 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-beta in various liver disease stages. We emphasise that, in order to achieve therapeutic effects, we need to target TGF-beta signalling in the right cell type at the right time.