晚期糖基化终产物对足细胞synaptopodin和迁移性的影响  

Effects of advanced glycation end-products on expression of synaptopodin and podocyte migration

作　　者：成彩联[1] 郑振达[1] 汤颖[1] 叶增纯[1] 李灿明[1] 娄探奇[1] 

机构地区：[1]中山大学附属第三医院肾内科,广州510630

出　　处：《第三军医大学学报》2013年第20期2199-2202,共4页Journal of Third Military Medical University

基　　金："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(2011B080701005;2010B031600202)~~

摘　　要：目的观察晚期糖基化终产物(advanced glycation end-products,AGEs)对足细胞synaptopodin的影响和在足细胞迁移性中的作用,探讨其作用机制。方法不同浓度AGEs(0、20、40、80μg/mL)干预足细胞24 h,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细胞迁移实验检测足细胞的迁移性,氯沙坦(100μmol/L)预处理足细胞后,观察synaptopodin和F-actin的改变。结果 AGEs 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。Objective To investigate the effects of advanced glycation end-products（AGEs） on the expression of synaptopodin and podocyte migration, and to explore their mechanisms. Methods Podocytes were incubated with different concentrations of AGEs （0，20，40 and 80 μg/mL）for 24 h, the expression levels of synaptopodin were measured by Western blotting, and cytoskeleton reorganization were observed by laser scanning confocal microscopy. Podocyte migration were assayed by Transwell assay.Then podocytes were pretreated with losartan for 60 min, and the changes of synaptopodin and cytoskeleton were observed. Results Incubation with AGEs resulted in a significant decrease in the expression of synaptopodin[（50±11）% vs 100%, P〈0.05] , AGEs also induced F-actin reorganization and increased podocyte migration（47±6 vs 13±3, P〈0.05）. However, pretreatment with losartan （100 μmol/L）alleviated the effects induced by AGEs in podocytes. Conclusions AGEs downregulate the expression of synaptopodin,induce cytoskeleton reorganization, and increase podocyte migration via activation the local renin-angiotensin system in podocytes.

关 键 词：晚期糖基化终产物 足细胞 SYNAPTOPODIN 迁移性 

分 类 号：R322.61[医药卫生—人体解剖和组织胚胎学] R329.28[医药卫生—基础医学]