| Role of epimorphin in bile duct formation of rat liver epithelial stem-like cells: Involvement of small G protein RhoA and C/EBPβ. | |
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MedLine Citation:
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PMID: 21935930 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yali Jia; Hailei Yao; Junnian Zhou; Lin Chen; Quan Zeng; Hongfeng Yuan; Lei Shi; Xue Nan; Yunfang Wang; Wen Yue; Xuetao Pei |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of cellular physiology Volume: 226 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-09-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 2807-16 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Wiley-Liss, Inc. |
Affiliation:
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Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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