Premature Aging in Skeletal Muscle Lacking Serum Response Factor 英文参考文献.docVIP

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Premature Aging in Skeletal Muscle Lacking Serum Response Factor 英文参考文献.doc

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Premature Aging in Skeletal Muscle Lacking Serum Response Factor 英文参考文献

PrematureAginginSkeletalMuscleLackingSerum ResponseFactor CharlotteLahoute1,2,AthanassiaSotiropoulos1,2,MarilyneFavier1,2,IsabelleGuillet-Deniau1,2 ,Claude Charvet3,ArnaudFerry4,5,GillianButler-Browne4,DanielMetzger6,DavidTuil1,2* ,Dominique Daegelen1,2 * 1Institut Cochin, Universite′ Paris Descartes, CNRS (UMR 8104), Paris, France, 2Inserm, U567, Paris, France, 3INRA, UR1282 Infectiologie Animale et Sante′ Publique, Nouzilly,France,4UMRS787,Inserm/UPMC-Paris6/InstitutdeMyologie,Paris,France,5Universite′ ParisDescartes,Paris,France,6IGBMC(InstitutdeGe′ne′tiqueetde BiologieMole′culaireetCellulaire),DepartmentofFunctionalGenomics,Inserm,U596,CNRS,UMR7104,Colle`ge deFrance,Illkirch,Universite′ LouisPasteur,Strasbourg, France Abstract Agingisassociatedwithaprogressivelossofmusclemass,increasedadiposityandfibrosisthatleadstosarcopenia.Atthe molecular level, muscle aging is known to alter the expression of a variety of genes but very little is known about the molecular effectors involved. SRF (Serum Response Factor) is a crucial transcription factor for muscle-specific gene expressionandforpost-natalskeletalmusclegrowth.Toassessitsroleinadultskeletalmusclephysiology,wedevelopeda post-mitoticmyofiber-specificandtamoxifen-inducibleSRFknockoutmodel.FivemonthsafterSRFloss,noobviousmuscle phenotypewasobservedsuggestingthatSRFisnotcrucialformyofibermaintenance.However,mutantmiceprogressively developedIIBmyofiber-specificatrophyaccompaniedbyametabolicswitchtowardsamoreoxidativephenotype,muscular lipidaccumulation,sarcomeredisorganizationandfibrosis.Afterinjury,mutantmusclesexhibitedanalteredregeneration process, showing smaller regenerated fibers and persistent fibrosis. All of these features are strongly reminiscent of abnormalitiesencounteredinagingskeletalmuscle.Interestingly,wealsoobservedanimportantageassociateddecrease in SRF expression in mice and human muscles. Altogether, these results suggest that a naturally occurring SRF down- regulationprecedesandcon