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Cell Tissue Res. 2012 Jan;347(1):245-56. doi: 10.1007/s00441-011-1246-y. Epub 2011 Oct 19.

TGF-β in progression of liver disease.

Author information

1
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

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.

PMID:
22006249
PMCID:
PMC3250614
DOI:
10.1007/s00441-011-1246-y
[Indexed for MEDLINE]
Free PMC Article

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