Published online Jul 14, 2017. doi: 10.3748/wjg.v23.i26.4661
Peer-review started: February 1, 2017
First decision: March 20, 2017
Revised: April 4, 2017
Accepted: May 19, 2017
Article in press: May 19, 2017
Published online: July 14, 2017
Processing time: 167 Days and 10.6 Hours
The question whether epithelial-mesenchymal transition (EMT) occurs during liver fibrogenesis is a controversial issue. In vitro studies confirm that hepatocytes or cholangiocytes undergo EMT upon transforming growth factor β (TGF-β) stimulation, whereas in vivo experiments based on genetic fate mapping of specific cell populations suggest that EMT does not occur in fibrotic animal models. In this review we present current data supporting or opposing EMT in chronic liver disease and discuss conditions for the occurrence of EMT in patients. Based on the available data and our clinical observations we hypothesize that EMT-like alterations in liver cirrhosis are a side effect of high levels of TGF-β and other pro-fibrotic mediators rather than a biological process converting functional parenchyma, i.e., hepatocytes, into myofibroblasts at a time when essential liver functions are deteriorating.
Core tip: This review provides a personal notion about whether a complete epithelial-mesenchymal transition (EMT) occurs in human fibrotic livers. We consider three aspects that might determine the occurrence of EMT: (1) capacity of parenchymal cells; (2) potential benefit for the liver and the whole body; and (3) microenvironment within a fibrotic liver. Clinical evidence suggests that in humans, EMT-like alterations occur mainly in advanced chronic liver disease, i.e., cirrhosis. In such a severe disease state, the most urgent mission for a liver is to maintain a maximum number of functional hepatocytes, while hepatic stellate cells and portal fibroblasts provide an ample supply of myofibroblasts. It appears that there is no need for additional sources of myofibroblasts in a cirrhotic liver. EMT-like alterations in parenchymal cells are most likely a side effect of high levels of EMT-promoting factors such as TGF-β.