Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells.
Understanding how hepatic precursor cells can generate differentiated bile ducts is crucial for studies on epithelial morphogenesis and for development of cell therapies for hepatobiliary diseases. Epimorphin (EPM) is a key morphogen for duct morphogenesis in various epithelial organs. The role of E...
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oai:doaj.org-article:4000d8e41f30450a8221bf1b33477dd22021-11-25T06:25:23ZEpimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells.1932-620310.1371/journal.pone.0009732https://doaj.org/article/4000d8e41f30450a8221bf1b33477dd22010-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20305811/?tool=EBIhttps://doaj.org/toc/1932-6203Understanding how hepatic precursor cells can generate differentiated bile ducts is crucial for studies on epithelial morphogenesis and for development of cell therapies for hepatobiliary diseases. Epimorphin (EPM) is a key morphogen for duct morphogenesis in various epithelial organs. The role of EPM in bile duct formation (DF) from hepatic precursor cells, however, is not known. To address this issue, we used WB-F344 rat epithelial stem-like cells as model for bile duct formation. A micropattern and a uniaxial static stretch device was used to investigate the effects of EPM and stress fiber bundles on the mitosis orientation (MO) of WB cells. Immunohistochemistry of liver tissue sections demonstrated high EPM expression around bile ducts in vivo. In vitro, recombinant EPM selectively induced DF through upregulation of CK19 expression and suppression of HNF3alpha and HNF6, with no effects on other hepatocytic genes investigated. Our data provide evidence that EPM guides MO of WB-F344 cells via effects on stress fiber bundles and focal adhesion assembly, as supported by blockade EPM, beta1 integrin, and F-actin assembly. These blockers can also inhibit EPM-induced DF. These results demonstrate a new biophysical action of EPM in bile duct formation, during which determination of MO plays a crucial role.Junnian ZhouLei ZhaoLipeng QinJing WangYali JiaHailei YaoChen SangQinghua HuShuangshuang ShiXue NanWen YueFengyuan ZhuangChun YangYunfang WangXuetao PeiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 3, p e9732 (2010) |
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Medicine R Science Q Junnian Zhou Lei Zhao Lipeng Qin Jing Wang Yali Jia Hailei Yao Chen Sang Qinghua Hu Shuangshuang Shi Xue Nan Wen Yue Fengyuan Zhuang Chun Yang Yunfang Wang Xuetao Pei Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells. |
description |
Understanding how hepatic precursor cells can generate differentiated bile ducts is crucial for studies on epithelial morphogenesis and for development of cell therapies for hepatobiliary diseases. Epimorphin (EPM) is a key morphogen for duct morphogenesis in various epithelial organs. The role of EPM in bile duct formation (DF) from hepatic precursor cells, however, is not known. To address this issue, we used WB-F344 rat epithelial stem-like cells as model for bile duct formation. A micropattern and a uniaxial static stretch device was used to investigate the effects of EPM and stress fiber bundles on the mitosis orientation (MO) of WB cells. Immunohistochemistry of liver tissue sections demonstrated high EPM expression around bile ducts in vivo. In vitro, recombinant EPM selectively induced DF through upregulation of CK19 expression and suppression of HNF3alpha and HNF6, with no effects on other hepatocytic genes investigated. Our data provide evidence that EPM guides MO of WB-F344 cells via effects on stress fiber bundles and focal adhesion assembly, as supported by blockade EPM, beta1 integrin, and F-actin assembly. These blockers can also inhibit EPM-induced DF. These results demonstrate a new biophysical action of EPM in bile duct formation, during which determination of MO plays a crucial role. |
format |
article |
author |
Junnian Zhou Lei Zhao Lipeng Qin Jing Wang Yali Jia Hailei Yao Chen Sang Qinghua Hu Shuangshuang Shi Xue Nan Wen Yue Fengyuan Zhuang Chun Yang Yunfang Wang Xuetao Pei |
author_facet |
Junnian Zhou Lei Zhao Lipeng Qin Jing Wang Yali Jia Hailei Yao Chen Sang Qinghua Hu Shuangshuang Shi Xue Nan Wen Yue Fengyuan Zhuang Chun Yang Yunfang Wang Xuetao Pei |
author_sort |
Junnian Zhou |
title |
Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells. |
title_short |
Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells. |
title_full |
Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells. |
title_fullStr |
Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells. |
title_full_unstemmed |
Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells. |
title_sort |
epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doaj.org/article/4000d8e41f30450a8221bf1b33477dd2 |
work_keys_str_mv |
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1718413737521577984 |