MicroRNAs Profiling in Murine Models of Acute and Chronic Asthma A Relationship with mRNAs Targets 英文参考文献.docVIP

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MicroRNAs Profiling in Murine Models of Acute and Chronic Asthma A Relationship with mRNAs Targets 英文参考文献.doc

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MicroRNAs Profiling in Murine Models of Acute and Chronic Asthma A Relationship with mRNAs Targets 英文参考文献

MicroRNAsProfilinginMurineModelsofAcuteand ChronicAsthma:ARelationshipwithmRNAsTargets NancyGarbacki1.,EmmanuelDiValentin2.,Va?nAnhHuynh-Thu3,PierreGeurts3,AlexandreIrrthum3, Ce′lineCrahay4,ThierryArnould5,ChristopheDeroanne1,JacquesPiette2,DidierCataldo4,AlainColige1* 1GIGA-Research,LaboratoryofConnectiveTissuesBiology,UniversityofLie`ge, Lie`ge,Belgium,2GIGA-Research,LaboratoryofVirologyandImmunology,Universityof Lie`ge,Lie`ge,Belgium,3GIGA-Research,Systemsandmodeling,UniversityofLie`ge,Lie`ge,Belgium,4GIGA-Research,LaboratoryofBiologyofTumoursandDevelopment, UniversityofLie`ge,Lie`ge,Belgium,5LaboratoryofBiochemistryandCellBiology,UniversityofNamur,Namur,Belgium Abstract Background: miRNAs are now recognized as key regulator elements in gene expression. Although they have been associatedwithanumberofhumandiseases,theirimplicationinacuteandchronicasthmaandtheirassociationwithlung remodellinghaveneverbeenthoroughlyinvestigated. Methodology/PrincipalFindings:InordertoestablishamiRNAsexpressionprofileinlungtissue,miceweresensitizedand challengedwithovalbuminmimickingacute,intermediateandchronichumanasthma.LevelsoflungmiRNAswereprofiled bymicroarrayandinsilicoanalyseswereperformedtoidentifypotentialmRNAtargetsandtopointoutsignallingpathways and biological processes regulated by miRNA-dependent mechanisms. Fifty-eight, 66 and 75 miRNAs were found to be significantly modulated at short-, intermediate- and long-term challenge, respectively. Inverse correlation with the expressionofpotentialmRNAtargetsidentifiedmmu-miR-146b,-223,-29b,-29c,-483,-574-5p,-672and-690asthebest candidatesforanactiveimplicationinasthmapathogenesis.Afunctionalvalidationassaywasperformedbycotransfecting inhumanlungfibroblasts(WI26)syntheticmiRNAsandengineeredexpressionconstructscontainingthecodingsequence ofluciferaseupstreamofthe39UTRofvariouspotentialmRNAtargets.ThebioinformaticsanalysisidentifiedmiRNA-linked regulationofseveralsignallingpathways,asmatrixmetalloproteinases,inflammatoryresp