However, the etiology of liver fibrosis includes viruses (hepatitis B and C viruses), alcohol intoxication, obesity, diabetes, and hereditary metabolism disorders, and so could the currently prevalent liver fibrosis models truly reflect the changes of the hepatocytes in liver injury? The existence of EMT of hepatocytes in liver fibrosis still seems to be an open question. With triple transgenic mice ROSA26 stop β-gal, AlbCre, and collagenase green fluorescent
protein (GFP), the double-positive cells for GFP and X-gal were not observed in situ at different stages of liver injury, including the chronic phase (after 16 injections with
CCl4), indicating collagen-producing cells do not originate from hepatocytes. The authors further demonstrated http://www.selleckchem.com/products/PD-0332991.html the isolated hepatocytes from CCl4-induced transgenic mice do not express mesenchymal markers including α-smooth muscle actin. However, in our CCl4-induced mouse liver fibrosis sections, α-smooth muscle actin was detected in the cytoplasm of hyperplastic hepatocytes by immunohistochemistry even though it is expressed prominently in the perisinusoidal space (Fig. 1). Therefore, we suggest the authors should evaluate see more again the double staining for myofibroblastic phenotypes and X-gal in situ. Recently, Zulehner et al. reported EMT is involved in hepatocarcinogenesis in a mouse model and loss of plasma
membrane E-cadherin expression in poorly differentiated human hepatocellular carcinoma, suggesting EMT of hepatocytes in this stage.5 Cirrhotic liver–derived hepatocytes from a mouse cirrhosis model with characteristics of EMT exhibit decreased apoptosis via a mitogen-activated protein kinase–dependent cell survival pathway, implying EMT as an outcome of antiapoptosis in carcinogenesis.6, 7 Because of the insufficient evidence from the literature and limitations of the study as mentioned by the authors, more detailed studies with a translational medicine methodology are needed to verify the existence of EMT of hepatocytes followed by investigation of its selleck related role in liver diseases, including liver fibrosis and hepatocellular carcinoma development. Da-Wei Zhang*, Huijie Bian*, * Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, China. “
“To the Editor We read with great interest the findings described by Shi et al. They detected high levels of donor-derived CD56+, CD3+, and CD14+ T cells in the first explanted liver grafts in both the short and long term after liver transplantation (LT).