MicroRNA Profiling in Subventricular Zone after Stroke MiR-124a Regulates Proliferation of Neural Progenitor Cells through Notch Signaling Pathway 英文参考文献.docVIP

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MicroRNA Profiling in Subventricular Zone after Stroke MiR-124a Regulates Proliferation of Neural Progenitor Cells through Notch Signaling Pathway 英文参考文献.doc

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MicroRNA Profiling in Subventricular Zone after Stroke MiR-124a Regulates Proliferation of Neural Progenitor Cells through Notch Signaling Pathway 英文参考文献

MicroRNAProfilinginSubventricularZoneafterStroke: MiR-124aRegulatesProliferationofNeuralProgenitor CellsthroughNotchSignalingPathway XianShuangLiu1,MichaelChopp1,2,RuiLanZhang1,TangTao1,XinLiWang1,HaifaKassis1 ,Ann Hozeska-Solgot1,LiZhang1,CharlesChen1,ZhengGangZhang1* 1DepartmentofNeurology,HenryFordHospital,Detroit,Michigan,UnitedStatesofAmerica,2DepartmentofPhysics,OaklandUniversity,Rochester,Michigan,United StatesofAmerica Abstract Background: The Notch signaling pathway regulates adult neurogenesis under physiological and pathophysiological conditions.MicroRNAsaresmallnon-codingRNAmoleculesthatregulategeneexpression.Thepresentstudyinvestigated theeffectofmiR-124aontheNotchsignalingpathwayinstroke-inducedneurogenesis. MethodologyandPrincipalFindings:Wefoundthatadultratssubjectedtofocalcerebralischemiaexhibitedsubstantial reductionofmiR-124aexpression,aneuronspecificmiRNA,intheneuralprogenitorcellsofthesubventricularzone(SVZ)of the lateral ventricle, which was inversely associated with activation of Notch signals. In vitro, transfection of neural progenitor cells harvested from the SVZ of adult rat with miR-124a repressed Jagged-1 (JAG1), a ligand of Notch, in a luciferaseconstructcontainingtheJAG1targetsite.IntroductionofmiR-124ainneuralprogenitorcellssignificantlyreduced JAG1transcriptandproteinlevels,leadingtoinactivationofNotchsignals.TransfectionofneuralprogenitorcellswithmiR- 124asignificantlyreducedprogenitorcellproliferationandpromotedneuronaldifferentiationmeasuredbyanincreasein the number of Doublecortin positive cells, a marker of neuroblasts. Furthermore, introduction of miR-124a significantly increasedp27Kip1mRNAandproteinlevels,adownstreamtargetgeneoftheNotchsignalingpathway. Conclusions:Collectively,ourstudydemonstratedthatinvivo,strokealtersmiRNAexpressioninSVZneuralprogenitorcells andthatinvitro,miR-124amediatesstroke-inducedneurogenesisbytargetingtheJAG-Notchsignalingpathway. Citation:LiuXS,ChoppM,ZhangRL,TaoT,WangXL,etal.(2011)MicroRNAProfili