Blocking TGFβ via Inhibition of the αvβ6 Integrin A Possible Therapy for Systemic Sclerosis Interstitial Lung Disease英文文献资料.docVIP

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Blocking TGFβ via Inhibition of the αvβ6 Integrin A Possible Therapy for Systemic Sclerosis Interstitial Lung Disease英文文献资料.doc

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Blocking TGFβ via Inhibition of the αvβ6 Integrin A Possible Therapy for Systemic Sclerosis Interstitial Lung Disease英文文献资料

HindawiPublishingCorporation InternationalJournalofRheumatology Volume2011,ArticleID208219,7pages doi:10.1155/2011/208219 ReviewArticle BlockingTGFβviaInhibitionoftheαvβ6Integrin:APossible TherapyforSystemicSclerosisInterstitialLungDisease TamikoR.Katsumoto, SheliaM.Violette, andDeanSheppard 1 2 1 1 2 DepartmentofMedicine,CriticalCare,AllergyandSleepMedicine,UniversityofCalifornia,SanFrancisco,CA94143,USA Stromedix,Cambridge,MA02141,USA CorrespondenceshouldbeaddressedtoTamikoR.Katsumoto,tamiko.katsumoto@ Received27May2011;Accepted15August2011 AcademicEditor:OliverDistler Copyright?2011TamikoR.Katsumotoetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Interstitiallungdisease(ILD)isacommonlyencounteredcomplicationofsystemicsclerosis(SSc)andaccountsforasigni?cant proportionofSSc-associatedmorbidityandmortality.Itspathogenesisremainspoorlyunderstood,andtherapiesthattreatSSc ILDaresuboptimal,atbest.SScILDpathogenesismaysharesomecommonmechanismswithother?broticlungdiseases,in whichdysregulationoflungepitheliumcancontributetopathologic?brosisviarecruitmentorinsitugenerationandactivation of?broblasts.TGFβ,amasterregulatorof?brosis,istightlyregulatedinthelungbytheintegrinαvβ6,whichisexpressedatlow levelsonhealthyalveolarepithelialcellsbutishighlyinducedinthesettingoflunginjuryor?brosis.Herewediscussthebiology ofαvβ6andpresentthisintegrinasapotentiallyattractivetargetforinhibitioninthesettingofSScILD. 1.Introduction e?ectorcellsthatareultimatelyinvolvedintheproduction ofcollagenandotherextracellularmatrix(ECM)proteins. However, the development of ?brosis in SSc is indeed a complex process involving crosstalk amongst multiple cell types, including epithelial, endothelial, immune, and mes- enchymalcelltypes.Inidiopathicpulmonary?brosis(IPF),a progressive?brosinglungdiseasethathasamediansurvival o