Estrogen Receptor Alpha Expression in Podocytes Mediates Protection against Apoptosis In-Vitro and In-Vivo 英文参考文献.docVIP

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Estrogen Receptor Alpha Expression in Podocytes Mediates Protection against Apoptosis In-Vitro and In-Vivo 英文参考文献.doc

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Estrogen Receptor Alpha Expression in Podocytes Mediates Protection against Apoptosis In-Vitro and In-Vivo 英文参考文献

EstrogenReceptorAlphaExpressioninPodocytes MediatesProtectionagainstApoptosisIn-Vitroand In-Vivo SebastianKummer1*,StefanieJeruschke1,2,LaraVanessaWegerich1,AndreaPeters1,PetraLehmann3, AnnetteSeibt1,FriederikeMueller6,NadezdaKoleganova3,ElisabethHalbenz6,ClausPeterSchmitt5, MarkusBettendorf4,ErtanMayatepek1,Marie-LuiseGross-Weissmann3,JunOh1,6 1DepartmentofGeneralPediatricsandNeonatology,UniversityChildren’sHospitalDuesseldorf,Duesseldorf,Germany,2PediatricNephrology,PediatricsII,Universityof Duisburg-Essen,Essen,Germany,3InstituteofPathology,UniversityHospitalHeidelberg,Heidelberg,Germany,4DivisionofPediatricEndocrinologyandDiabetology, UniversityChildren’sHospital,Heidelberg,Germany,5DivisionofPediatricNephrology,UniversityChildren’sHospital,Heidelberg,Germany,6DepartmentofPediatric Nephrology,UniversityMedicalCenter,Hamburg-Eppendorf,Hamburg,Germany Abstract Context/Objective:Epidemiologicalstudieshavedemonstratedthatwomenhaveasignificantlybetterprognosisinchronic renaldiseasescomparedtomen.Thissuggestscriticalinfluencesofgenderhormonesonglomerularstructureandfunction. Weexaminedpotentialdirectprotectiveeffectsofestradiolonpodocytes. Methods:Expressionofestrogenreceptoralpha(ERa)wasexaminedinpodocytesinvitroandinvivo.Receptorlocalization was shown using Western blot of separated nuclear and cytoplasmatic protein fractions. Podocytes were treated with Puromycinaminonucleoside(PAN,apoptosisinduction),estradiol,orbothincombination.Apoptoticcellsweredetected with Hoechst nuclear staining and Annexin-FITC flow cytometry. To visualize mitochondrial membrane potential depolarization as an indicator for apoptosis, cells were stained with tetramethyl rhodamine methylester (TMRM). Estradiol-inducedphosphorylationofERK1/2andp38MAPKwasexaminedbyWesternblot.GlomeruliofERaknock-out miceandwild-typecontrolswereanalysedbyhistomorphometryandimmunohistochemistry. Results: ERa was consistently expressed in human and murine podocytes. Estradiol stimulated ERa protein expression,