微rna133和心肌肥厚钙调磷酸酯酶控制的相互抑制（英文）

ReciprocalRepressionbetweenMicroRNA 133andCalcineurinControlsCardiacHypertrophy ANovelMechanismforProgressiveCardiacHypertrophy De LiDong Yan JieLu Bao FengYang 董德利吕延杰杨宝峰 DepartmentofPharmacologyHarbinMedicalUniversity P R China Aug 20 22 2009 Dalian Background Calcineurin NFATpathwayinducesCardiacHypertrophyCalcineurinactivationincardiachypertrophyDecreasedmiR 133expressionincardiachypertrophyOverexpressionofmiR 133inhibitscardiachypertrophyInhibitionofmiR 133inducescardiachypertrophy Aug 20 22 2009 Dalian 1 Calcineurin DependentCardiacHypertrophy JefferyD Molkentinetal Cell 1998 93 215 228 Aug 20 22 2009 Dalian 1 Calcineurin DependentCardiacHypertrophy JefferyD Molkentinetal Cell 1998 93 215 228 Aug 20 22 2009 Dalian 1 Calcineurin DependentCardiacHypertrophy JefferyD Molkentinetal Cell 1998 93 215 228 Aug 20 22 2009 Dalian OverexpressionofcalcineurininmousecausessuddencardiacdeathassociatedwithdecreaseddensityofKchannels DeliDong etal CardiovascularResearch57 2003 320 332 Aug 20 22 2009 Dalian 2 CalcineurinActivationincardiachypertrophy HaeW Limetal Circulation 2000 101 2431 2437 Aug 20 22 2009 Dalian 3 Calcineurin NFATCouplingParticipatesinPathological butnotPhysiological CardiacHypertrophy WilkinsBJ etal CircRes 2004 94 110 118 Aug 20 22 2009 Dalian Car Aetal NatMed 2007 13 5 613 8 4 DecreasedmiR 133expressionincardiachypertrophy Aug 20 22 2009 Dalian 5 OverexpressionofmiR 133inhibitscardiachypertrophy Car Aetal NatMed 2007 13 5 613 8 Aug 20 22 2009 Dalian 6 InhibitionofmiR 133inducescardiachypertrophy Car Aetal NatMed 2007 13 5 613 8 Aug 20 22 2009 Dalian Hypothesis InteractionbetweenmiR 133andcalcineurinincardiachypertrophy CalcineurinisthetargetofmiR 133 TheexpressionofmiR 133isregulatedbycalcineurin NFATsignalingpathway Calcineurin miR 133 Cardiachypertrophy Aug 20 22 2009 Dalian Results1 miR 133TargetsCalcineurin Figure1 Post transcriptionalRepressionofCalcineurinbymiR 133 A ThesequencesshowingtheuniquesitesofmiRNA mRNAcomplementarybetweenmiR 133andcalcineurinforratandmousegenes B Co transfectionofmiR 133withtheluciferasereportergenelinkedtothe3 UTRofcalcineurinreducedluciferaseactivityinratandmousespecies P 0 01vsControl P 0 05vsmiR 133 0 0 5 1 0 Relativeluciferaseactivity 0 0 5 1 0 NC miR 133 AMO 133 miR 133 AMO 133 Mut 133 B Mouse n 8 Rat n 10 A Aug 20 22 2009 Dalian Results miR 133TargetsCalcineurin Fig 2 A transfectionofmiR 133specificallyincreasedmiR 133levelinculturedcardiomyocytes P 0 01vsnon transfectiongroup B Thenegativecontrol NC hadnoeffectonmiR 133level butAMO 133decreasedmiR 133level P 0 01vscontrol lipofectaminetransfectionagents n 3 A B Aug 20 22 2009 Dalian Results miR 133TargetsCalcineurin Fig 3 EffectsofmiR 133oncalcineurinproteinlevels n 5 mRNAlevel n 5 andcellarea Thenumberwasinbrackets innormalculturedcardiomyoctes P 0 01vsControl Aug 20 22 2009 Dalian A B C 1 miR 133TargetsCalcineurin Figure4 EffectsofmiR 133oncalcineurinproteinlevels n 5 mRNAlevel n 5 andcellarea Thenumberofcellswasinbrackets incardiomyoctestreatedwithPE 50 M A B C Aug 20 22 2009 Dalian Results Calcineurin NFATSignalingRegulatesmiR 133Expression Fig 5 CalcineurininhibitorCsAinhibitedcardiachypertrophyinducedbytransverseaorticconstrictioninmice Sham TAC TAC CsA Aug 20 22 2009 Dalian A B Results Calcineurin NFATSignalingRegulatesmiR 133Expression Fig 6 CalcineurininhibitorCsAinhibitedcardiachypertrophy Thenumberwasinbrackets calcineurinexpression n 5 andactivity n 5 P 0 01vsControl P 0 01vsTAC Aug 20 22 2009 Dalian A B C Results Calcineurin NFATSignalingRegulatesmiR 133Expression Fig 7 CsArestoredthedecreasedmiR 133expressionbutnottheincreasedmiR 195expressioninTAC inducedhypertrophicheart P 0 01vsControl P 0 01vsTAC n 5 Aug 20 22 2009 Dalian A B Results Calcineurin NFATSignalingRegulatesmiR 133Expression Fig 8 Primaryratscardiomyocytesinserum freemediumwerestimulatedwithPEandPE CsA Cardiomyocyteswereidentifiedwitha actininantibody redsignal andnucleiwerestainedwithbis benzamide blue Control PE PE CsA Aug 20 22 2009 Dalian A B Results Calcineurin NFATSignalingRegulatesmiR 133Expression Fig 9 CsAinhibitedhypertrophy Thenumberwasinbrackets calcineurinexpression n 5 andactivity n 5 incardiomyocytestreatedwithPE 50 M P 0 01vsControl P 0 01vsPE Aug 20 22 2009 Dalian A B C Results Calcineurin NFATSignalingRegulatesmiR 133Expression Fig 10 CsAalleviatedthedecreasedmiR 133expressioninPE treatedcardiomyocyes P 0 01vsControl P 0 05vsPE n 5 Aug 20 22 2009 Dalian Results Calcineurin NFATSignalingRegulatesmiR 133Expression Fig 11 Calcineurin NFAT dependentRegulationofmiR 133 A Antisense A ODNsincreasedtheexpressionofmiR 133inculturedcardiomyocytes P 0 01vsControl n 4 B NFATdecoyODNsincreasedtheexpression