Epithelial-mesenchymal transition in chronic liver disease: fibrogenesis or escape from death?

The possibility that epithelial-mesenchymal transition (EMT) could contribute to hepatic fibrogenesis in chronic liver diseases as reported in other organs, particularly the kidney, reinforced the concept that activated hepatic stellate cells were not the only key players in the hepatic fibrogenic process and that other cell types, either hepatic (i.e. portal fibroblast) or extrahepatic (bone marrow-derived cells and circulating fibrocytes) could contribute to this process. The possibility of the rapid mobilization of a large amount of fibrogenic cells by EMT after liver tissue injury made this phenomenon a relevant and suitable target for anti-fibrogenic strategies. Following an initial enthusiasm for the discovery of this novel pathway in fibrogenesis and the publication of a several highly quoted papers, more recent research has started to cast serious doubts upon the real relevance of this phenomenon in human fibrogenetic disorders. The debate on the authenticity of EMT or at least on its real contribution to the fibrogenic process has become very animated, sometimes reaching levels of "religious" integralism. The overall result is a general confusion on the meaning and on the definition of several key aspects. The aim of this article is to analyze and discuss the evidence supporting or confuting this possibility in order to reach reasonable and useful conclusions.