Can a fibrotic liver afford epithelial-mesenchymal transition?

Table 1 Selected evidence supporting or opposing epithelial-mesenchymal transition during liver fibrogenesis

	Ref.
Supporting evidence
In vitro
Primary cultured hepatocytes or cholangiocytes with TGF-β stimulation undergo complete EMT	[4,21,23-27,29,30]
Patients
Liver parenchymal cells in patients with advanced chronic liver disease express mesenchymal markers	[17,19-22,30]
Opposing evidence
Techniques based on genetic cell fate mapping of specific cell populations provided convincing evidence that EMT does not occur in fibrotic animal models	[4,5,10]
Clinical observation
There is no data showing that parenchymal cells of patients express mesenchymal markers during early stages of fibrosis
Parenchymal cells expressing mesenchymal markers are found only in patients with advanced chronic liver disease, e.g., cirrhosis. A cirrhotic liver is not likely to drive remaining parenchymal cells towards a non-essential biological process like EMT
No studies indicate that activation of HSC, portal fibroblasts and fibrocytes produce insufficient MFB
In the cirrhotic liver, parenchymal cells expressing mesenchymal markers might be caused by high levels of surrounding pro-EMT factors, e.g., TGF-β

TGF-β: Transforming growth factor β; EMT: Epithelial-mesenchymal transition; HSC: Hepatic stellate cells; MFB: Myofibroblasts.