Prolyl Isomerase Pin1 Regulates Mouse Embryonic Fibroblast Differentiation into Adipose Cells 英文参考文献.docVIP

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Prolyl Isomerase Pin1 Regulates Mouse Embryonic Fibroblast Differentiation into Adipose Cells 英文参考文献.doc

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Prolyl Isomerase Pin1 Regulates Mouse Embryonic Fibroblast Differentiation into Adipose Cells 英文参考文献

ProlylIsomerasePin1RegulatesMouseEmbryonic FibroblastDifferentiationintoAdiposeCells TakafumiUchida1,2*,KengoFurumai1,TomokazuFukuda3,HirotadaAkiyama1,2,MikaTakezawa1, TomoichiroAsano4,FumihiroFujimori2,5,ChiyokoUchida2,6 1MolecularEnzymology,DepartmentofMolecularCellScience,GraduateSchoolofAgriculturalScience,TohokuUniversity,Miyagi,Japan,2CenterforInterdisciplinary Research,TohokuUniversity,Miyagi,Japan,3DepartmentofAnimalProductionScience,TohokuUniversity,Miyagi,Japan,4DepartmentofMedicalScience,Hiroshima University,Hiroshima,Japan,5DepartmentofEnvironmentalEducation,TokyoKaseiUniversity,Tokyo,Japan,6UniversityHealthCenter,IbarakiUniversity,Mito,Japan Abstract Background: A peptidyl prolyl cis/trans isomerase, Pin1, regulates insulin signal transduction. Pin1 reduces responses to insulinstimulationbybindingCRTC2(CREB-regulatedtranscriptionalco-activator2)andPPARc(peroxisomeprolifereator- activatedreceptorc),butconverselyenhancesinsulinsignalingbybindingIRS-1(insulinreceptorsubstrate-1),Aktkinase, andSmad3.Therefore,itisstillunclearwhetherPin1inhibitsorenhancesadiposecelldifferentiation. Methodology/PrincipalFindings:Pin12/2andwild-typemicewerefedwithhighfatdietsandadiposetissueweightwas measured.Comparedtowild-typemice,Pin12/2micehadloweradiposetissueweight,whiletheweightofothertissues was similar. Mouse embryo fibroblasts (MEFs), prepared from both groups of mice, were induced to differentiate into adiposecellsbystimulationwithinsulin.However,therateofdifferentiationofMEFsfromPin12/2micewaslessthanthat ofMEFsfromwild-typemice.Therateofinsulin-inducedMEFcelldifferentiationinPin12/2micewasrestoredbyincreasing expressionofPin1.WefoundthatPin1bindstophosphoThr172-andphosphoSer271-PrositesinCREBsuppresstheactivity inCOS-7cells. ConclusionandSignificance:Pin1enhancedtheuptakeoftriglyceridesandthedifferentiationofMEFcellsintoadipose cells in response to insulin stimulation. Results of this study suggest that Pin1 down-regulation could be a potential approachinobesity