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《Clusterin_apolipoprotein J attenuates angiotensin II-induced renal fibrosis.》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、Clusterin/ApolipoproteinJAttenuatesAngiotensinII-InducedRenalFibrosis1.1.2121Gwon-SooJung,Jae-HanJeon,Yun-AJung,Yeon-KyungChoi,Hye-SoonKim,Jung-GukKim,121Keun-GyuPark,Mi-KyungKim*,In-KyuLee*1DivisionofEndocrinologyandMetabolism,DepartmentofInternalMedicine,KyungpookNationalUniversitySchoolofMedicine
2、,Daegu,RepublicofKorea,2DivisionofEndocrinologyandMetabolism,DepartmentofInternalMedicine,KeimyungUniversitySchoolofMedicine,Daegu,RepublicofKoreaAbstractTheblockadeofangiotensinII(AngII)isamajortherapeuticstrategyfordiabeticnephropathy.ThemainrolesofAngIIinrenaldiseasearemediatedviatheAngtype1recep
3、tor(AT1R).Upregulationofclusterin/apolipoproteinJhasbeenreportedinnephropathymodels,suggestingithasaprotectiveroleinnephropathogenesis.Here,westudiedhowclusterinactsagainstAngII-inducedrenalfibrosis.LevelsofAT1Randfibroticmarkersinclusterin-/-miceandAngIIinfusedratstransfectedwithanadenovirusencodin
4、gclusterinwereevaluatedbyimmunoblotanalysis,realtimeRT-PCR,andimmunohistochemicalstaining.TheeffectofclusterinonrenalfibrosiswasevaluatedinNRK-52Ecells,aculturedrenaltubularepithelialcellline,usingimmunoblotanalysisandrealtimeRT-PCR.NuclearlocalizationofNF-kBwasevaluatedusingimmunofluorecenceandco-i
5、mmunoprecipitation.RenalfibrosisandexpressionofAT1Rwashigherinthekidneysof-/-clusterinmicethaninthoseofwild-typemice.Furthermore,lossofclusterinacceleratedAngII-stimulatedrenalfibrosisandAT1Rexpression.OverexpressionofclusterininproximaltubularepithelialcellsdecreasedthelevelsofAngII-stimulatedfibro
6、ticmarkersandAT1R.Moreover,intrarenaldeliveryofclusterinattenuatedAngII-mediatedexpressionoffibroticmarkersandAT1Rinrats.Fluorescencemicroscopyandco-immunoprecipitationinconjunctionwithwesternblotrevealedthatclusterininhibitedAngII-stimulatednuclearlocalizationofp-NF-kBviaadirectphysicalinteractiona
7、ndsubsequentlydecreasedtheAT1Rlevelinproximaltubularepithelialcells.ThesedatasuggestthatclusterinattenuatesAngII-inducedrenalfibrosisbyinhibitionofNF-kBactivationandsubsequentdownregulationofAT1R.This
