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1、AdenosineReceptorExpressionintheDevelopmentofRenalFibrosisFollowingIschemicInjurya,b,aa,baV.Roberts*,B.Lu,K.M.Dwyer,andP.J.CowanabImmunologyResearchCentre,StVincent’sHospital,Melbourne,Victoria,Australia;andUniversityofMelbourne,Victoria,AustraliaABSTRACTLong-termrenalallograftsurvi
2、valhasnotimproveddespiteimprovementsinshorttermoutcomes.Graftlossischaracterizedhistologicallybythedevelopmentofinterstitialfibrosisandtubularatrophy(IFTA).MechanismsunderlyingthedevelopmentofIFTAaremultifactorialandincludeischemia-reperfusioninjury(IRI).TherapeuticoptionstoreduceIFT
3、Aincludemanagementofimmunologiccauses,suchasrejection,butdespitetheseeffortsIFTAcanstilloccurandleadstotheinexorabledestructionofthetransplantedkidney.TheadenosineA2Breceptor(A2BR)hasrecentlybeenimplicatedinthedevel-opmentofrenalfibrosis.WeperformedanobservationalstudytoexaminethemRN
4、AexpressionoftheadenosinereceptorsafterrenalischemiauptothedevelopmentofrenalfibrosisinamousemodelofunilateralIRI.A2BRwastheonlyadenosinereceptorthatshowedelevatedexpressionfollowingischemiauntilthedevelopmentofrenalfibrosis4weeksafterinjury.At2weeksafterischemia,increasedexpressionof
5、thefibroticmarkerstransforminggrowthfactorbandCollagen-1awasobserved.Expressionofhypoxiainduciblefactor1aandendothelin-1,whichliedownstreamofA2BRactivationandhavebeenrecognizedtopromoterenalfibrosis,werealsosignificantlyup-regulatedat2weeksafterischemia.Expressionoffibroticmarkersreturn
6、edtobaselineby4weeksafterischemia,indicatingresolutionofinjurywiththeconcurrentdevelopmentofrenalfibrosisandreducedrenalfunction.OurdatasuggestthatA2BRmaybeatherapeutictargetinreducingthedevelopmentofrenalfibrosisafterischemia.ENALtransplantationisthepreferredtreatmentforrenalfibrosisi
7、nmousemodelsofangiotensin-inducedRpatientswithend-stagekidneydisease,butthereisahypertension[2,3]andunilateraluretericobstruction[3].largedisparitybetweentheavailabilityofdonororgansandtheLeeetal[4]recentlyreportedthattheexpressionofall4numberofpatientsawaitingtransplantation.Inanat
8、tempttoadenosinerec
