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1、晚期糖基化终产物对足细胞synaptopodin和迁移性的影响成彩联,郑振达,汤颖汤颖,叶增纯,李灿明,娄探奇(510630广州,中山大学附属第三医院肾内科)[摘要]目的观察晚期糖基化终产物(AGEs)对足细胞synaptopodin和迁移性的影响及作用机制方法不同浓度AGEs(0,20,40,80μg/mL)干预足细胞24小时,免疫印迹检测足细胞synaptopodin的表达,激光共聚焦显微镜观察足细胞肌动蛋白F-actin和synaptopodin的分布,Transwell细胞迁移试验检测足细胞的迁移性,氯沙坦预处理足细胞后,观察synaptopodin和F-actin的改变。结果AG
2、Es(80μg/mL)可降低足细胞synaptopodin的表达[(50±11)%vs.100%,P<0.05],并使肌动蛋白骨架F-actin发生重构,足细胞的迁移性增高[(47±6)vs.(13±3),P<0.05],氯沙坦可减轻AGEs介导的synaptopodin的下调[(80±12)%vs.(50±11)%,P<0.05]和F-actin的的重构,降低足细胞的迁移性[(25±4)vs.(47±6),P<0.05]。结论AGEs可能通过激活足细胞内的肾素-血管紧张素系统的机制,下调synaptopodin表达,介导骨架蛋白的重构,增加迁移性。[关键词]晚期糖基化终产物;足细胞;sy
3、naptopodin[基金项目]“十二五”国家科技支撑计划(2011BA110B05);国家自然科学基金(81070581);广东省科技厅基金资助项目(2011B080701005,2010B031600202)[通讯作者]娄探奇,E-mail:Lou.tq@163.comEffectsofadvancedglycationend-productsontheexpressionofsynaptopodinandinpodocytemigrationsChengcailian,Zhengzhenda,TangYingTangYing,Yezengchun,Licanming,Loutanqi
4、.(DepartmentofNephrology,TheThirdAffiliatedHospitalofSunYat-senUniversity,Guangdong,Guangzhou510630)AbstractObjectToinvestigatetheeffectsofadvancedglycationend-products(AGEs)ontheexpressionofsynaptopodinand,podocytemigration,andtheirmechanisms.theirmechanism.MethodsPodocyteswereincubatedwithdiffer
5、entconcentrationsofAGEsfor24hours,theexpressionlevelsofsynaptopodinweremeasuredbywesternblot,cytoskeletonreorganizationwereobservedbylaser10scanningconfocalmicroscopy.Podocytemigrationwereassayedbytranswellassay.Thenpodocyteswerepretreatedwithlosartanfor60min,thechangesofsynaptopodinandcytoskeleto
6、nwereobserved.ResultsIncubationwithAGEsresultedinasignificantdecreaseintheexpressionofsynaptopodin[(50±11)%vs.100%,P<0.05],AGEsalsoinducedF-acinreorganizationandincreasedpodocytemigration[(47±6)vs.(13±3),P<0.05].However,pretreatmentwithangiotensinⅡreceptorblockerlosartan(100μmol/L)alleviatedtheeff
7、ectsinducedbyAGEsinpodocytes.ConclusionsAGEsupregulatetheexpressionofsynaptopodinandinducecytoskeletonreorganizationviaactivationthelocalrenin-angiotensinsysteminpodocytes.Keywords:advancedglycationend-products;p