Sox17 Promotes Cell Cycle Progression and Inhibits TGF-βSmad3 Signaling to Initiate Progenitor Cell Behavior in the Respiratory Epithelium 英文参考文献.docVIP

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Sox17 Promotes Cell Cycle Progression and Inhibits TGF-βSmad3 Signaling to Initiate Progenitor Cell Behavior in the Respiratory Epithelium 英文参考文献.doc

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Sox17 Promotes Cell Cycle Progression and Inhibits TGF-βSmad3 Signaling to Initiate Progenitor Cell Behavior in the Respiratory Epithelium 英文参考文献

Sox17PromotesCellCycleProgressionandInhibits TGF-b/Smad3SignalingtoInitiateProgenitorCell BehaviorintheRespiratoryEpithelium AlexanderW.Lange1,AngelaR.Keiser1,JamesM.Wells2,AaronM.Zorn2,JeffreyA.Whitsett1* 1DivisionofPulmonaryBiology,CincinnatiChildren’sHospitalMedicalCenter andtheUniversityofCincinnatiCollegeofMedicine,Cincinnati,Ohio, UnitedStates of America,2DivisionofDevelopmentalBiology,CincinnatiChildren’sHospitalMedicalCenterandtheUniversityofCincinnatiCollegeofMedicine,Cincinnati,Ohio,United StatesofAmerica Abstract TheSry-relatedhighmobilitygroupboxtranscriptionfactorSox17isrequiredfordiversedevelopmentalprocessesincluding endodermformation,vasculardevelopment,andfetalhematopoieticstemcellmaintenance.ExpressionofSox17inmature respiratory epithelial cells causes proliferation and lineage respecification, suggesting that Sox17 can alter adult lung progenitorcellfate.Inthispaper,weidentifymechanismsbywhichSox17influenceslungepithelialprogenitorcellbehavior andreprogramscellfateinthematurerespiratoryepithelium.ConditionalexpressionofSox17inepithelialcellsoftheadult mouselungdemonstratedthatcellclusterformationandrespecificationofalveolarprogenitorcellstowardproximalairway lineageswererapidlyreversibleprocesses.ProlongedexpressionofSox17causedtheectopicformationofbronchiolar-like structureswithdiverserespiratoryepithelialcellcharacteristicsinalveolarregionsoflung.Duringinitiationofprogenitorcell behavior,Sox17inducedproliferationandincreasedtheexpressionoftheprogenitorcellmarkerSca-1andgenesinvolvedin cellcycleprogression.Notably,Sox17enhancedcyclinD1expressioninvivoandactivatedcyclinD1promoteractivityinvitro. Sox17decreasedtheexpressionoftransforminggrowthfactor-beta(TGF-b)-responsivecellcycleinhibitorsintheadultmouse lung,includingp15,p21,andp57,andinhibitedTGF-b1-mediatedtranscriptionalresponsesinvitro.Further,Sox17interacted withSmad3andblockedSmad3DNAbindingandtranscriptionalactivity.Together,thesedatashowthatasubsetofmature respiratory epitheli