Editorial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2017; 23(26): 4661-4668
Published online Jul 14, 2017. doi: 10.3748/wjg.v23.i26.4661
Can a fibrotic liver afford epithelial-mesenchymal transition?
Stefan Munker, Yong-Le Wu, Hui-Guo Ding, Roman Liebe, Hong-Lei Weng
Stefan Munker, Roman Liebe, Hong-Lei Weng, Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
Stefan Munker, Department of Medicine I, University Medical Center, Regensburg University, 93053 Regensburg, Germany
Yong-Le Wu, Hui-Guo Ding, Department of Gastroenterology and Hepatology, Beijing You’an Hospital affiliated to Capital Medical University, Beijing 100069, China
Hui-Guo Ding, Major infectious diseases Collaborative Innovation Center, Beijing 100069, China
Roman Liebe, Department of Medicine II, Saarland University Medical Center, Saarland University, 66123 Homburg, Germany
Author contributions: Weng HL conceived and designed the manuscript; Munker S, Wu YL, Ding HG, Liebe R and Weng HL wrote and edited the manuscript.
Supported by Munker S, Weng HL were supported by Chinese-German Cooperation Group project, No. GZ 1263; Ding HG was supported by the National Science Fund, No. 81672725; the Capital Science and Technology Development Fund, No. 2014-1-2181; and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding, No. ZYLX201610.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hong-Lei Weng, PhD, Principle Investigator, Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany. honglei.weng@medma.uni-heidelberg.de
Telephone: +49-621-3835603 Fax: +49-621-3831467
Received: January 25, 2017
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
Abstract

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.

Keywords: Epithelial-mesenchymal transition, Liver fibrosis, Liver cirrhosis, Transforming growth factor-β

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.