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Role of epimorphin in bile duct formation of rat liver epithelial stem-like cells: Involvement of small G protein RhoA and C/EBPβ.
MedLine Citation:
PMID:  21935930     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Epimorphin/syntaxin 2 is a high conserved and very abundant protein involved in epithelial morphogenesis in various organs. We have shown recently that epimorphin (EPM), a protein exclusively expressed on the surface of hepatic stellate cells and myofibroblasts of the liver, induces bile duct formation of hepatic stem-like cells (WB-F344 cells) in a putative biophysical way. Therefore, the aim of this study was to present some of the molecular mechanisms by which EPM mediates bile duct formation. We established a biliary differentiation model by co-culture of EPM-overexpressed mesenchymal cells (PT67(EPM) ) with WB-F344 cells. Here, we showed that EPM could promote WB-F344 cells differentiation into bile duct-like structures. Biliary differentiation markers were also elevated by EPM including Yp, Cx43, aquaporin-1, CK19, and gamma glutamyl transpeptidase (GGT). Moreover, the signaling pathway of EPM was analyzed by focal adhesion kinase (FAK), extracellular regulated kinase 1/2 (ERK1/2), and RhoA Western blot. Also, a dominant negative (DN) RhoA-WB-F344 cell line (WB(RhoA-DN) ) was constructed. We found that the levels of phosphorylation (p) of FAK and ERK1/2 were up-regulated by EPM. Most importantly, we also showed that RhoA is necessary for EPM-induced activation of FAK and ERK1/2 and bile duct formation. In addition, a dual luciferase-reporter assay and CHIP assay was performed to reveal that EPM regulates GGT IV and GGT V expression differentially, possibly mediated by C/EBPβ. Taken together, these data demonstrated that EPM regulates bile duct formation of WB-F344 cells through effects on RhoA and C/EBPβ, implicating a dual aspect of this morphoregulator in bile duct epithelial morphogenesis. J. Cell. Physiol. 226: 2807-2816, 2011. © 2011 Wiley-Liss, Inc.
Authors:
Yali Jia; Hailei Yao; Junnian Zhou; Lin Chen; Quan Zeng; Hongfeng Yuan; Lei Shi; Xue Nan; Yunfang Wang; Wen Yue; Xuetao Pei
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  226     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-09-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2807-16     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Affiliation:
Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.
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