Erk1 and Erk2 Regulate Endothelial Cell Proliferation and Migration during Mouse Embryonic Angiogenesis 英文参考文献.docVIP

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Erk1 and Erk2 Regulate Endothelial Cell Proliferation and Migration during Mouse Embryonic Angiogenesis 英文参考文献.doc

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Erk1 and Erk2 Regulate Endothelial Cell Proliferation and Migration during Mouse Embryonic Angiogenesis 英文参考文献

Erk1andErk2RegulateEndothelialCellProliferationand MigrationduringMouseEmbryonicAngiogenesis RuchikaSrinivasan1,2,TaheraZabuawala1,2,HongHuang3,JianyingZhang4,ParulGulati4 ,Soledad Fernandez4,J.ColleenKarlo5,GaryE.Landreth5,GustavoLeone2,6,MichaelC.Ostrowski1,2 * 1Department ofMolecularandCellularBiochemistry,TheOhioStateUniversity,Columbus,Ohio,UnitedStatesofAmerica, 2TumorMicroenvironmentProgram,The ComprehensiveCancerCenter,TheOhioStateUniversity,Columbus,Ohio,UnitedStatesofAmerica,3CenterforCardiovascularMedicine,NationwideChildren’sHospital, Columbus,Ohio,UnitedStatesofAmerica,4CenterforBiostatistics,TheOhioStateUniversity,Columbus,Ohio,UnitedStatesofAmerica,5DepartmentofCellularand Molecular Neuroscience, Case Western Reserve University, Cleveland, Ohio, United States of America, 6Department of Molecular Virology, Immunology and Medical Genetics,andDepartmentofMolecularGenetics,TheOhioStateUniversity,Columbus,Ohio,UnitedStatesofAmerica Abstract Angiogenesis is a complex process orchestrated by both growth factors and cell adhesion and is initiated by focal degradationofthevascularbasementmembranewithsubsequentmigrationandproliferationofendothelialcells.TheRas/ Raf/MEK/ERKpathwayisrequiredforECfunctionduringangiogenesis.AlthoughinvitrostudiesimplicateERK1andERK2in endothelialcellsurvival,theirpreciseroleinangiogenesisinvivoremainspoorlydefined.Cre/loxPtechnologywasusedto inactivateErk1andErk2inendothelialcellsduringmurinedevelopment,resultinginembryoniclethalityduetoseverely reduced angiogenesis. Deletion of Erk1 and Erk2 in primary endothelial cells resulted in decreased cell proliferation and migration,butnotinincreasedapoptosis.Expressionofkeycellcycleregulatorswasdiminishedinthedoubleknockout cells,anddecreasedDNAsynthesiscouldbeobservedinendothelialcellsduringembryogenesis.Interestingly,bothPaxillin andFocalAdhesionKinasewereexpressedatlowerlevelsinendothelialcellslackingErk1andErk2bothinvivoandinvitro, leadingtodefectsintheorganizationofthecytos