Calreticulin Is a Negative Regulator of Bronchial Smooth Muscle Cell Proliferation英文文献资料.docVIP

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Calreticulin Is a Negative Regulator of Bronchial Smooth Muscle Cell Proliferation英文文献资料.doc

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Calreticulin Is a Negative Regulator of Bronchial Smooth Muscle Cell Proliferation英文文献资料

HindawiPublishingCorporation JournalofAllergy Volume2012,ArticleID783290,7pages doi:10.1155/2012/783290 ResearchArticle CalreticulinIsaNegativeRegulatorof BronchialSmoothMuscleCellProliferation NicolaMiglino,MichaelRoth,DidierLardinois,MichaelTamm,andPeterBorger DepartmentsofBiomedicine,PulmonaryCellResearch,andThoraxSurgery,UniversityHospitalBasel,Hebelstrasse20, 4031Basel,Switzerland CorrespondenceshouldbeaddressedtoNicolaMiglino,nicola.miglino@unibas.ch Received26July2011;Revised1November2011;Accepted23November2011 AcademicEditor:IreneHeijink Copyright?2012NicolaMiglinoetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Background. Calreticulin controls the C/EBPαp42/p30 at the translational level trough a cis-regulatory CNG rich loop in the CEBPAmRNA.Wedeterminedthee?ectsofsteroidsandlong-acting beta-agonistsonthep42/p30ratioandoncalreticulin expressioninprimaryhumanbronchialsmoothmuscle(BSM)cells.Methods.Thee?ectsofbudesonide(10?8M)andformoterol (10 ?8M)werestudiedinBSMcellspre-treatedwithsiRNAtargetingcalreticulin.TheexpressionofC/EBPαandcalreticulinwas determinedbyimmuno-blotting.Automatedcellcountswereperformedtomeasureproliferation.Results.AlltestedBSMcelllines (n=5)expressedC/EBPαandcalreticulin.Inthepresenceof5%FBS,thep42/p30ratiosigni?cantlydecreased(n=3,P0.05) andcoincidedwithBSMcellproliferation.Highlevelsofcalreticulinwereassociatedwithadecreasedp42/p30isoformratio.FBS inducedtheexpressionofcalreticulin(n=3,P0.05),whichwasfurtherincreasedbyformoterol.siRNAtargetingcalreticulin increasedthep42/p30ratioinnon-stimulatedBSMcellsandsigni?cantlyinhibitedtheproliferationofPDGF-BB-stimulated BSMcells(n=5,P0.05).Neitherbudesonidenorformoterolrestoredthep42isoformexpression.Conclusions.Ourdatashow calreticulinisanegativeregulatorofC/EBPαproteinexpressioninBSMcells.Modulationofcalreticulinlevelsmayprovideanovel target