, Volume 347, Issue 1, pp 245-256,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 19 Oct 2011

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.

Our studies of the role of TGF-β in fibrosis are supported by the Netherlands Institute for Regenerative Medicine (NIRM), the Netherlands Organisation for Scientific Research (NWO-MW), the Centre for Biomedical Genetics (PtD), the German Research Foundation with the programs SFB TRR77 Liver Cancer TP A6 and Do373/8-1 and BMBF grants (The Virtual Liver and Cell Therapy in Liver Regeneration).