The3rdlnternationalSymposiumonCarcinogenicSpiral&
IntemationalSymposiumonTumol･BiologyinKanazawa
B i o l o g i c a l f i m c t i o n o f p a r a c e l l u l a r b a r r i e r ‑ f O r m i n g c l a u d i n s a n d c l a u d i n ‑ d e f i c i e n c y ‑ r e l a t e d m e t a p l a S i a
SachikoTbukita
Lα加ﾉworyqfBiojogic"JScie"ce,Gﾉ･qd"αreSc/zooIqf届℃""e7・
Bioscie"ces""dGﾉ･ad""eSc/IooIqfMedici"eosq"U>zive"izy Ifz版α血o",S""α5"‑087/,J"pα〃
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Epithelialcellsheetscovertheouterandinnersurfacesofeverycompartmentinthebody,at everylevel,fifomthecelltothebodysulface,andtheyfilnctionatalloftheselevelsasa permselectivebarrier.Theparacellularbarrier,whichisestablishedbythefbrmationoftight junctionsbetweenepithelialcells,isbasicallybuiltbythepolymerizationofclaudins.Thus, claudinsarethoughttoplayaroleinthemicroenvironmentfbrvariousbiologicalfimctions.
Analysesofclaudinknockoutmicearebeginningtoelucidatethephysiologicalrelevanceofthe paracellularbarriers/permeabilityinmanybiologicalsystems.Singleormultipleclaudinshave beentargetedindifferentcombinations.
Defectsinthetightjunction(TJ)epithelialparacellularbarrierfUnctionarethoughttobea primarycauseofinflammation,butthemechanismremainslargelyunknown.Hereweexamined theinflammationreactionsassociatedwiththeknockoutmiceofclaudin‑18,amajorcomponentof
T J s i n t h e s t o m a c h . T h e C M z / 8/ ‑ m i c e w e r e a f f l i c t e d w i t h a t r o p h i c g a s t r i t i s , w h i c h s t a r t e d o n p o s t n a t a l d a y ( p n d ) 3 , w h e n t h e i n t r a g a s t r i c p H w a s d e c r e a s e d b y H + s e c r e t i o n f r o m p a r i e t a l c e l l s , concomitantwiththeup‑regulationoflL‑18,COX‑2,andKC.Theseconditionsinduced
spasmolyticpolypeptide‑expressingmetaplasia(SPEM)andintestinalmetaplasia(1M),although theprolongedacuteinflammationdidnotdevelopintochronicinflammation.Weexamnedwhichconditions,suchasincreasedcellproliferationintheCId"18/‑mce,mightleadtochronic
inflannnation.ThesefindingsmayprovideanewparadigmfOrunderstandingtheregulationof
inflammation.
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Session30ncoprotein&TumorSuppressor2
15:55〜16:20
SachikOTbukita
Professor,LaboratoryofBiologicalScience・GraduateSchoolofFrontier BiosciencesandGraduateSchoolofMedicine,OsakaUniversity,Japan E‑mail:atsukita@biosci.med・osaka‑u.acjp
雷 … − ー 一 . . −
￨"UCMIOMSMFRANNG
ぬ1976 1978 1983
Universityof'Ibkyo,FacultyofPhannaceuticalSciences,Japan(BPhann) UniversityofTbkyo,FacultyofPhannaceuticalSciences,Japan(MPharm) UniversityofTbkyo,DepartmentofAnatomy,FacultyofMedicine,Japan(PhD)
ROSXIYONSANDHONORS
1983‑1986 1986‑1990
ResearchAssociate,DepartmentofAnatomy,UniversityofTbkyo,FacultyofMedicine,Japan
ResearchAssociate,DepartmentofUltrastructuralResearch,TbkyoMetropolitanInstituteofMedical Science,Japan
AssistantProfessor,DepartmentoflnfbnnationPhysiology,NationallnstitutefbrPhysiologicalSciences, Japan
Professor,CollegeofMedicalTbchnology,KyotoUniversity,Japan
Professor,SchoolofHealthSciences,FacultyofMedicine,KyotoUniversity,Japan
Professor,LaboratolyofBiologicalScience,GraduateSchoolofFrontierBiosciences/Departmentof Pathology,GraduateSchoolofMedicine,OsakaUniversity,Japan
1990‑1994
1994‑2003 2003‑2007 2007.4‑Present
ｔｔ
ｎｎ ｅｅＳＳ ｅｅｒｒ
ｐｐ室画９００１００２２ManagingDirectolJCouncil,JapaneseSocietyofBiologicalChemistry Steering/Audit,JapaneseSocietyofCellBiology
W E 華
RECENTPUBEICArIONS
l.ItohM,TbukitaS,YamazakiY,andSugimotoH.RhoGTPexchangefactorARHGEFllregulatestheintegrityof epithelialjunctionsbyconnectingZO‑landRhoA‑myosinllsignalingProcⅣα"A"dSciUSA,109:9905‑9910,2012.
2.KunimotoK,YamazakiY;NishidaT,ShinoharaK,IshikawaH,HasegawaT,OkanoueT,HamadaH,NodaT,'Itlmura A,TbukitaS,andTbukitaS.LossofbasalfeetondeletionoftwoexonsofOdf2perturbspolarizationofbasalbodiesin multiciliatedcells.Ce",148:189‑200,2012.
3.HayashiD,'IamuraA,TanakaH,YamazakiY,WatanabeS,SuzukiK,SuzukiK,SentaniK,YasuiW,RakugiH,Isaka Y,andTbukitaS.Deficiencyofclaudin‑18causesparacellularH+leakage,up‑regulationofinterleukin‑lbetaand atrophicgastritisinmice.G""りe"膨Jりゎgy,142:292‑304,2011.
4YanoT,YamazakiYJAdachiM,OkawaK,FortP,UjiM,TbukitaS,andTbukitaS.Tｾlraup‑regulatesE‑cadherin transcriptionbybindingtotheTrioRhoGEFandinhibitingRac‑signaling.JCe"BioZ,193:319‑332,2011.
5.YamazakiY,TbkumasuR,KimuraH,andTbukitaS.Roleofclaudinspecies‑specificdynamicsinreconstitutionand remodelingofthezonulaoccludens.MoIBioICe",22:1495‑1504,2011.
6.通muraA,HayashiH,ImasatoM,YamazakiY,HagiwaraA,WadaM,NodaT,WatanabeM,SuzukiY,andTbukitaSa.
Lossofclaudin‑15,butnotclaudin‑2,causesNa+deficiencyandglucosemalabsorptioninmousesmallintestine G""･0e""70Iogy,140:913‑923,2010.
7.NqimaH,AdachiM,MatsuiT,OkawaK,'IbukitaS,andTbukitaS.IQGAP3regulatescellprolifErationthroughthe Ras/ERKsignallingcascade.N"Ce"Bi01,10:971‑978,2008.
8.YamazakiYjUmedaK,WadaM,NadaS,OkadaM,'IbukitaS,andTbukitaS.ZO‑l/2‑dependentIntegrationofMyosin‑
2toEpithelialZonulaAdherens.MoIBioICell,19:3801‑3811,2008.
9.UmedaK,IkenouchiJ,Katahira声nyamaS,FuruseK,SasakiH,NakayamaM,MatsuiT,TbukitaS,FuruseM,and TbukitaS.ZO‑1andZO‑2independentlydetelminewhereclaudinsarepolymerizedintightjunctionstrandfbrmation.
Ce",126:741‑754,2006.
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