Epimorphin Regulates Bile Duct Formation via Effects on Mitosis Orientation in Rat Liver Epithelial Stem-Like Cells 英文参考文献.docVIP

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Epimorphin Regulates Bile Duct Formation via Effects on Mitosis Orientation in Rat Liver Epithelial Stem-Like Cells 英文参考文献.doc

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Epimorphin Regulates Bile Duct Formation via Effects on Mitosis Orientation in Rat Liver Epithelial Stem-Like Cells 英文参考文献

EpimorphinRegulatesBileDuctFormationviaEffectson MitosisOrientationinRatLiverEpithelialStem-LikeCells JunnianZhou1.,LeiZhao2.,LipengQin1,JingWang2,YaliJia1,HaileiYao1,ChenSang2,QinghuaHu2, ShuangshuangShi1,XueNan1,WenYue1,FengyuanZhuang2,ChunYang2*¤,YunfangWang1* ,Xuetao Pei1* 1StemCellandRegenerative MedicineLab, BeijingInstitute ofTransfusionMedicine,Beijing, China, 2SchoolofBiologicalScienceandMedicalEngineering, Beihang University,Beijing,China Abstract Understanding how hepatic precursor cells can generate differentiated bile ducts is crucial for studies on epithelial morphogenesisandfordevelopmentofcelltherapiesforhepatobiliarydiseases.Epimorphin(EPM)isakeymorphogenfor ductmorphogenesisinvariousepithelialorgans.TheroleofEPMinbileductformation(DF)fromhepaticprecursorcells, however,isnotknown.Toaddressthisissue,weusedWB-F344ratepithelialstem-likecellsasmodelforbileductformation. AmicropatternandauniaxialstaticstretchdevicewasusedtoinvestigatetheeffectsofEPMandstressfiberbundlesonthe mitosis orientation (MO) of WB cells. Immunohistochemistry of liver tissue sections demonstrated high EPM expression aroundbileductsinvivo.Invitro,recombinantEPMselectivelyinducedDFthroughupregulationofCK19expressionand suppressionofHNF3aandHNF6,withnoeffectsonotherhepatocyticgenesinvestigated.Ourdataprovideevidencethat EPMguidesMOofWB-F344cellsviaeffectsonstressfiberbundlesandfocaladhesionassembly,assupportedbyblockade EPM,b1integrin,andF-actinassembly.TheseblockerscanalsoinhibitEPM-inducedDF.Theseresultsdemonstrateanew biophysicalactionofEPMinbileductformation,duringwhichdeterminationofMOplaysacrucialrole. Citation:ZhouJ,ZhaoL,QinL,WangJ,JiaY,etal.(2010)EpimorphinRegulatesBileDuctFormationviaEffectsonMitosisOrientationinRatLiverEpithelial Stem-LikeCells.PLoSONE5(3):e9732.doi:10.1371/journal.pone.0009732 Editor:JosephNajbauer,CityofHopeNationalMedicalCenter,UnitedStatesofAmerica ReceivedOctober27,2009;AcceptedFebruary23,2010;PublishedMarch17,2010 Copyright: ? 2010 Zhou et al