TGF-β in progression of liver disease
Top Cited Papers
Open Access
- 19 October 2011
- journal article
- review article
- Published by Springer Science and Business Media LLC in Cell and tissue research
- Vol. 347 (1), 245-256
- https://doi.org/10.1007/s00441-011-1246-y
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.Keywords
This publication has 111 references indexed in Scilit:
- Hedgehog signaling in the liverJournal of Hepatology, 2011
- Liver regeneration: Alternative epithelial pathwaysThe International Journal of Biochemistry & Cell Biology, 2011
- Lineage tracing demonstrates no evidence of cholangiocyte epithelial-to-mesenchymal transition in murine models of hepatic fibrosisJournal of Hepatology, 2011
- Regulation of liver regeneration by growth factors and cytokinesEMBO Molecular Medicine, 2010
- Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in miceJournal of Hepatology, 2009
- Targeting transforming growth factor-β signaling in liver metastasis of colon cancerCancer Letters, 2009
- Liver stem cells and hepatocellular carcinomaJournal of Hepatology, 2008
- TGFβ‐mediated BIM expression and apoptosis are regulated through SMAD3‐dependent expression of the MAPK phosphatase MKP2EMBO Reports, 2008
- Liver regenerationJournal of Cellular Physiology, 2007
- Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammationCell Metabolism, 2006