Notch-RBP-J Signaling Regulates the Mobilization and Function of Endothelial Progenitor Cells by Dynamic Modulation of CXCR4 Expression in Mice 英文参考文献.docVIP
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Notch-RBP-J Signaling Regulates the Mobilization and Function of Endothelial Progenitor Cells by Dynamic Modulation of CXCR4 Expression in Mice 英文参考文献
Notch-RBP-JSignalingRegulatestheMobilizationand
FunctionofEndothelialProgenitorCellsbyDynamic
ModulationofCXCR4ExpressioninMice
LinWang1,2.,Yao-ChunWang1.,Xing-BinHu1.,Bing-FangZhang1.,Guo-RuiDou1,FeiHe1,FangGao1,
FanFeng1,Ying-MinLiang1,Ke-FengDou2*,HuaHan1*
1StateKeyLaboratoryofCancerBiology,DepartmentofMedicalGeneticsandDevelopmentalBiology,Xi-JingHospital,FourthMilitaryMedicalUniversity,Xi’an,China,
2DepartmentofHepaticSurgery,Xi-JingHospital,FourthMilitaryMedicalUniversity,Xi’an,China
Abstract
Bonemarrow(BM)-derivedendothelialprogenitorcells(EPC)havetherapeuticpotentialsinpromotingtissueregeneration,
but how these cells are modulated in vivo has been elusive. Here, we report that RBP-J, the critical transcription factor
mediatingNotchsignaling,modulatesEPCthroughCXCR4.Inamousepartialhepatectomy(PHx)model,RBP-Jdeficient
EPCshowedattenuatedcapacitiesofhomingandfacilitatingliverregeneration.Inrestingmice,theconditionaldeletionof
RBP-JledtoadecreaseofBMEPC,withaconcomitantincreaseofEPCintheperipheralblood.Thiswasaccompaniedbya
down-regulation of CXCR4 on EPC in BM, although CXCR4 expression on EPC in thecirculation was up-regulated in the
absence of RBP-J. PHx in RBP-J deficient mice induced stronger EPC mobilization. In vitro, RBP-J deficient EPC showed
loweredcapacitiesofadhering,migrating,andformingvessel-likestructuresinthree-dimensionalcultures.Over-expression
ofCXCR4couldatleastrescuethedefectsinvesselformationbytheRBP-JdeficientEPC.Thesedatasuggestedthatthe
RBP-J-mediatedNotchsignalingregulatedEPCmobilizationandfunction,atleastpartiallythroughdynamicmodulationof
CXCR4 expression. Our findingsnot onlyprovide newinsights into theregulation ofEPC, but also haveimplications for
clinicaltherapiesusingEPCindiseases.
Citation:WangL,WangY-C,HuX-B,ZhangB-F,DouG-R,etal.(2009)Notch-RBP-JSignalingRegulatestheMobilizationandFunctionofEndothelialProgenitor
CellsbyDynamicModulationofCXCR4ExpressioninMice.PLoSONE4(10):e7572.doi:10.1371/journal.pone.0007572
Editor:PieterH.Re
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