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+112NSFCNSFC3NSFC4NSFC56NSFC1234RNAi56NSFC78NSFC9NSFC10NSFC1112SARS131415NSFC125000345idea678ScienceNatureAnnualReviews915101112131missionimpossible234567MTA12SCI123data4516-101-22-33-5231NSFC4125262NSFC7812345125%?5%360-70%410%105NSFC5NSFC6123451234NSFC5123545NSFC4000-80001NICUextracellularmatrix,ECMECMECMECMmatrixmetalloproteinasesMMPs(tissueinhibitorofmetalloproteinases,TIMPs)MMPsMMPs/TIMPsECM[1]MMPsECMMMPsMMPsextracellularmatrixmetalloproteinaseinducer,EmmprinMMPsEmmprin58KDEmmprin[2]EmmprinMMPsEmmprinMMPMAPKp38ECM[34]Emmprin/MAPKp38MMPsECMEmmprinMMPs/TIMPsTransforminggrowthfactorbeta,TGF-MMPsTGF-MMPs[5]TGF-MMP-1MMP-1[6]TGF-MMP-1SMADECM[5]TGF-/SMADMMPs/TIMPsECMECMTGF-MMPs/TIMPs50-100nmcaveolaecaveolin21-24kDcaveolincaveolin[7]caveolinECMcaveolincaveolin-1caveolin-1[8]caveolin1TGF-TRTGF-SMAD-2[9]EmmprinMAPKp38caveolinEmmprinEmmprinMAPKp38MMP/MMPsECMEmmprin/MAPKp38TGF-/SMADMMPsECM7.RamirezMI,PollackL,MillienG,etal.Thealpha-IsoformofCaveolin-1IsaMarkerofVasculogenesisinEarlyLungDevelopment.JHistochemCytochem2002;50(1):33~428.DrabM,VerkadeP,ElgerM,etal.Lossofcaveolae,vasculardysfunction,andpulmonarydefectsincaveolin-1gene-disruptedmice.Science2001;293(5539):2449~522,caveolin+?caveolin/EmmprinEmmprin/MAPKp38+caveolin/TRTGF-/SMADECMMMPs/TIMPsEGb761ECM1.TaylorPM,WoodfieldRJ,HodgkinMNetal.Breastcancercell-derivedEMMPRINstimulatesfibroblastMMP2releasethroughaphospholipaseA(2)and5-lipoxygenasecatalyzedpathway.Oncogene2002Aug22;21(37):5765-722.LiangL,MajorT,BocanT.Characterizationofthepromoterofhumanextracellularmatrixmetalloproteinaseinducer(EMMPRIN).Gene2002Jan9;282(1-2):75-863.LimM,MartineT,JablonsD.Tumor-derivedEMMPRIN(extrocellularmatrixmetalloproteinasesinducer)stimulatescollagenasetranscriptionthroughMAPKp38.FEBSLett1998;441(1):88~924.YuanW,VargaJ.Transforminggrowthfactor-betarepressionofmatrixmetalloproteinase-1indermalfibroblastsinvolvesSmad3.JBiolChem2001;276(42):38502-105.WhiteLA,MitchellTI,BrinckerhoffCE.Transforminggrowthfactorbetainhibitoryelementintherabbitmatrixmetalloproteinase-1(collagenase-1)genefunctionsasarepressorofconstitutivetranscription.BiochimBiophysActa2000Feb29;1490(3):259-686.RazaniB,ZhangXL,BitzerM,etal.Caveolin-1regulatesTGF-beta/SMADsignalingthroughaninteractionwiththeTGF-betatypeIreceptor.JBiolChem2001;276(9):6727~6738EmmprinTGF-MMPsECMEmmprin/MAPKp38TGF-/SMAD1.Emmprin/MAPKp38ECMEmmprinP38P38Emmprin/MAPKp38MMPs2.TGF-/SMADECMTGF-TRSMADSMADTRSMADSMADTGF-/SMADMMPs/TIMPs3.caveolin-1Emmprin/MAPKp38TGF-/SMADECMcaveolin-1caveolin-1Emmprincaveolin-1TR1.2.caveolinEmmprinEmmprin/MAPKp38caveolin-1TRTGF-/SMAD3confocalmicroscopeWesternBlotNorthernBlot1..caveolin-1caveolin-1pAbmAbWesternBlot.EmmprinP38P38TGF-TGF-TRSMAD-2SMADECMWesternBlotmRNANorthernBlotRT-PCR.TRTRimmunoprecipitionTRGST-SMAD2deCaestecher,MSMAD2TR.caveolin/Emmprincaveolin-1/TRcaveolinmAbPEEmmprin/TRpAbFITCTCSSPLeicacaveolinSAScaveolaecaveolinEmmprin/MAPKp38TGF-/SMADEmmprinP38P38TGF-TRSMADSMADNorthernBlotWesternBlotNorthernBlotRT-PCR)TR1.2.3.caveolin/Emmprincaveolin/TRcaveolin-14Emmprin/MAPKp38,caveolinEmmprin/MAPKp38TGF-/SMADcaveolin/Emmprincaveolin/TR53.20041~820049~2005220053~7MMPsTIMPsTGF-TRSMAD2mRNA20058~200512caveolin-1caveolin-1/TR20061~20066caveolin/Emprin()caveolin/TR()caveolin-120067~12ECMMMP/MMPsECMEmmprin/MAPKp38TGF-/SMADMMPsECM11.85%95%IL-8TGF-1.2.1.2.MMPs123MMP-23.BALF4.MMPsTIMPsMMP-2MMP-9TIMP-1TIMP-23dO20.460.360.900.642.000.470.300.23air0.070.100.070.160.870.580.030.087dO21.330.600.110.452.600.711.150.34air0.360.430.170.351.700.350.060.1014dO23.400.532.750.663.370.452.430.18air1.300.900.330.312.820.890.080.1021dO23.730.463.350.603.880.111.900.38air0.300.140.600.102.540.550.300.144P0.0521)2)Westernblotnorthernblot3)Caveolin-1DivisionofHematology/Oncology/BMTDepartmentofPediatricsEmoryUniversitySchoolofMedicineFokTF341EGB761TNF-IL-8IL-1IL-6MMPsTIMPsmRNA23