Matrix Metalloproteinase Gene Polymorphisms and Bronchopulmonary Dysplasia Identification of MMP16 as a New Player in Lung Development 英文参考文献.docVIP

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Matrix Metalloproteinase Gene Polymorphisms and Bronchopulmonary Dysplasia Identification of MMP16 as a New Player in Lung Development 英文参考文献.doc

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Matrix Metalloproteinase Gene Polymorphisms and Bronchopulmonary Dysplasia Identification of MMP16 as a New Player in Lung Development 英文参考文献

MatrixMetalloproteinaseGenePolymorphismsand BronchopulmonaryDysplasia:IdentificationofMMP16as aNewPlayerinLungDevelopment AliceHadchouel1,2,FabriceDecobert1,2,3,Marie-LaureFranco-Montoya1,2,IsabelleHalphen1,2 ,Pierre- HenriJarreau2,4,10,OlivierBoucherat1,2,EmmanuelMartin5,AlexandraBenachi1,2,6,SergeAmselem7, JacquesBourbon1,2,ClaudeDanan1,2,3,8,ChristopheDelacourt1,2,9 * 1INSERM,Unite′ 841,IMRB,e′quipe06,Cre′teil,France,2PremUp,Paris,France,3Re′animationNe′onatale,CentreHospitalierIntercommunal,Cre′teil,France,4Servicede me′decinene′onatale dePort-Royal,AP-HP,Ho?pitalCochin,Paris,France,5IntegraGen,Evry,France,6Serviced’Obste′triqueetGyne′cologie,AP-HP,Ho?pitalNecker,Paris, France,7INSERMU654,GHArmandTrousseau,Paris,France,8Unite′ FonctionnelledeRechercheClinique,CentreHospitalierIntercommunal,Cre′teil,France,9Universite′ Paris12,Faculte′ deMe′decine,IFR10,Cre′teil,France,10Universite′ ParisDescartes,Faculte′ deMe′decine, Paris,France Abstract Backgound: Alveolarization requires coordinated extracellular matrix remodeling, a process in which matrix metallopro- teinases(MMPs)playanimportantrole.WepostulatedthatpolymorphismsinMMPgenesmightaffectMMPfunctionin pretermlungsandthusinfluencetheriskofbronchopulmonarydysplasia(BPD). Methods and Findings: Two hundred and eighty-four consecutive neonates with a gestational age of ,28weeks were includedinthisprospectivestudy.Forty-fiveneonatesdevelopedBPD.Ninesingle-nucleotidepolymorphisms(SNPs)were soughtintheMMP2,MMP14andMMP16genes.Afteradjustmentforbirthweightandethnicorigin,theTTgenotypeof MMP16C/T(rs2664352)andtheGGgenotypeofMMP16A/G(rs2664349)werefoundtoprotectfromBPD.Thesegenotypes were also associated with a smaller active fraction of MMP2 and with a 3-fold-lower MMP16 protein level in tracheal aspiratescollectedwithin3daysafterbirth.FurtherevaluationofMMP16expressionduringthecourseofnormalhuman andratlungdevelopmentshowedrelativelylowexpressionduringthecanalicularandsaccularstagesandaclearincrease inbothmRNA