Activation of Fms-Like Tyrosine Kinase 3 Signaling Enhances Survivin Expression in a Mouse Model of Rheumatoid Arthritis 英文参考文献.docVIP

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Activation of Fms-Like Tyrosine Kinase 3 Signaling Enhances Survivin Expression in a Mouse Model of Rheumatoid Arthritis 英文参考文献.doc

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Activation of Fms-Like Tyrosine Kinase 3 Signaling Enhances Survivin Expression in a Mouse Model of Rheumatoid Arthritis 英文参考文献

ActivationofFms-LikeTyrosineKinase3Signaling EnhancesSurvivinExpressioninaMouseModelof RheumatoidArthritis SofiaE.M.Andersson*,MattiasN.D.Svensson,MalinC.Erlandsson,MatsDehlin,KarinM.E.Andersson, MariaI.Bokarewa DepartmentofRheumatologyandInflammationResearch,SahlgrenskaUniversityHospital,UniversityofGo¨teborg,Go¨teborg,Sweden Abstract Survivinisknownasaninhibitorofapoptosisandapositiveregulatorofcelldivision.Wehaverecentlyidentifiedsurvivinas apredictor ofjointdestruction inpatients withrheumatoidarthritis (RA).Flt3ligand(Flt3L)isexpressedin theinflamed joints and has adjuvant properties in arthritis. Studies on 90 RA patients (median age 60.5 years [range, 24–87], disease duration10.5years[range,0–35])showastrongpositiveassociationbetweenthelevelsofsurvivinandFlt3Linblood.Here, wepresentexperimentalevidenceconnectingsurvivinandFlt3Lsignaling.TreatmentofBALB/cmicewithFlt3Lledtoan increaseofsurvivininthebonemarrowandinsplenicdendriticcells.Flt3Lchangedtheprofileofsurvivinsplicevariants, increasingtranscriptionoftheshortsurvivin40inthebonemarrow.TreatmentwithanFlt3inhibitorreducedtotalsurvivin expressioninbonemarrowandinthedendriticcellpopulationinspleen.Inhibitionofsurvivintranscriptioninmice,by shRNAlentiviralconstructs,reducedthegeneexpressionofFlt3L.Weconcludethatexpressionofsurvivinisadownstream event of Flt3 signaling, which serves as an essential mechanism supporting survival of leukocytes during their differentiation,andmaturationofdendriticcells,inRA. Citation:AnderssonSEM,SvenssonMND,ErlandssonMC,DehlinM,AnderssonKME,etal.(2012)ActivationofFms-LikeTyrosineKinase3SignalingEnhances SurvivinExpressioninaMouseModelofRheumatoidArthritis.PLoSONE7(10):e47668.doi:10.1371/journal.pone.0047668 Editor:SergeNataf,UniversityofLyon,France ReceivedMarch14,2012;AcceptedSeptember18,2012;PublishedOctober17,2012 Copyright: ?2012 Andersson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrest