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《Vitamin D receptor attenuates renal fibrosis by suppressing the renin-angiotensin system.》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、BASICRESEARCHwww.jasn.orgVitaminDReceptorAttenuatesRenalFibrosisbySuppressingtheRenin-AngiotensinSystem†YanZhang,*JuanKong,*DilipK.Deb,*AnthonyChang,andYanChunLi*†Departmentsof*MedicineandPathology,DivisionofBiologicalSciences,UniversityofChicago,Chicago,IllinoisABSTRACTAnalogsofvitaminDattenuatere
2、nalinjuryinseveralmodelsofkidneydisease,butthemechanismunderlyingthisrenoprotectiveeffectisunknown.ToaddresstheroleofthevitaminDreceptor(VDR)inrenalfibrogenesis,wesubjectedVDR-nullmicetounilateralureteralobstructionfor7days.Comparedwithwild-typemice,VDR-nullmicedevelopedmoresevererenaldamageintheob
3、structedkidney,withmarkedtubularatrophyandinterstitialfibrosis.Significantinductionofextracellularmatrixproteins(fibronectinandcollagenI),profibrogenicandproinflammatoryfactors(TGF-,connectivetissuegrowthfactor,andmonocytechemoattractantprotein1),andepithelial-to-mesenchymaltransitionaccompaniedth
4、ishistologicdamage.BecauseVDRablationactivatestherenin-angiotensinsystemandleadstoaccumulationofangiotensinII(AngII)inthekidney,weassessedwhetherelevatedAngIIintheVDR-nullkidneypromotesinjury.Treatmentwiththeangiotensintype1antagonistlosartaneliminatedthedifferenceinobstruction-inducedinterstitialf
5、ibrosisbetweenwild-typeandVDR-nullmice,suggestingthatAngIIcontributestotheenhancedrenalfibrosisobservedinobstructedVDR-nullkidneys.Takentogether,theseresultssuggestthattheVDRattenuatesobstructiverenalinjuryatleastinpartbysuppressingtherenin-angiotensinsystem.JAmSocNephrol21:966–973,2010.doi:10.1681
6、/ASN.2009080872Interstitialfibrosisisahallmarkofchronicrenalfactors,isimportantfortheprogressionoftubulo-failureandstronglycorrelateswithdeteriorationofinterstitialfibrosis.3renalfunction,regardlessoftheunderlyingdisease.AngiotensinII(AngII)andTGF-aretwomajorUnilateralureteralobstruction(UUO)isawe
7、ll-es-fibrogenicfactorsthatmediatefibrogenesisinthekid-tablishedmodeloftubulointerstitialfibrosisoftheney.4Theintrarenalrenin-angiotensinsystem(RAS)kidney.Inthismodel,damageoftheobstructedisactivatedinobstr
