胆管上皮细胞
肌成纤维细胞
肝纤维化
上皮-间质转换
纤维化
肝星状细胞
病理
间充质
波形蛋白
癌症研究
祖细胞
转分化
间充质干细胞
生物
细胞生物学
化学
医学
下调和上调
干细胞
免疫组织化学
生物化学
基因
作者
Andrew S. Chu,Rosalyn Díaz,Jia–Ji Hui,Kilangsungla Yanger,Yiwei Zong,Gianfranco Alpini,Ben Z. Stanger,Rebecca G. Wells
出处
期刊:Hepatology
[Wiley]
日期:2011-01-27
卷期号:53 (5): 1685-1695
被引量:201
摘要
Whether or not cholangiocytes or their hepatic progenitors undergo an epithelial-to-mesenchymal transition (EMT) to become matrix-producing myofibroblasts during biliary fibrosis is a significant ongoing controversy. To assess whether EMT is active during biliary fibrosis, we used Alfp-Cre × Rosa26-YFP mice, in which the epithelial cells of the liver (hepatocytes, cholangiocytes, and their bipotential progenitors) are heritably labeled at high efficiency with yellow fluorescent protein (YFP). Primary cholangiocytes isolated from our reporter strain were able to undergo EMT in vitro when treated with transforming growth factor-β1 alone or in combination with tumor necrosis factor-α, as indicated by adoption of fibroblastoid morphology, intracellular relocalization of E-cadherin, and expression of α-smooth muscle actin (α-SMA). To determine whether EMT occurs in vivo, we induced liver fibrosis in Alfp-Cre × Rosa26-YFP mice using the bile duct ligation (BDL) (2, 4, and 8 weeks), carbon tetrachloride (CCl4) (3 weeks), and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC; 2 and 3 weeks) models. In no case did we find evidence of colocalization of YFP with the mesenchymal markers S100A4, vimentin, α-SMA, or procollagen 1α2, although these proteins were abundant in the peribiliary regions. Conclusion: Hepatocytes and cholangiocytes do not undergo EMT in murine models of hepatic fibrosis. (Hepatology 2011;)
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