糖基化终产物通过其受体诱导人肾小球系膜细胞表达CTGF和FN  

Advanced glycosylation end products induce CTGF and FN expression via their receptor RAGE in human renal mesangial cells

作　　者：冯敏[1] 黄国良[1] 李健榕[1] 钟林娜[1] 

机构地区：[1]福建医科大学附属协和医院内分泌科,福建省内分泌研究所,福建福州350001

出　　处：《中国病理生理杂志》2010年第6期1156-1160,共5页Chinese Journal of Pathophysiology

基　　金：福建医科大学教授发展基金资助项目(No.JS06085)

摘　　要：目的:探讨体外培养条件下糖基化终产物(AGEs)对人肾小球系膜细胞(HRMCs)中结缔组织生长因子(CTGF)及纤维连接蛋白(FN)基因表达的影响及其可能的作用机制。方法:将HRMCs与不同浓度的糖化牛血清白蛋白(AGE-BSA)和牛血清白蛋白(BSA)共同培养,或与同一质量浓度的AGE-BSA和BSA共同培养不同时间,以中和性抗RAGE抗体封闭细胞膜上糖基化终末产物受体(RAGE);采用免疫印迹法(Western blotting)观察AGEs对HRMCs中RAGE表达的影响,半定量逆转录-聚合酶链反应(RT-PCR)法检测CTGF、FN mRNA的表达。结果:在HRMCs中存在少量RAGE的表达,AGE-BSA能够诱导HRMCs中RAGE的表达增加,并以时间和剂量依赖方式促进HRMCs中CTGF和FN的表达上调;CTGF、FN的表达水平在加入不同浓度(50、100、200、400 mg/L)的AGE-BSA作用48 h后以及加入质量浓度为200 mg/L的AGE-BSA作用不同时间(12、24、48、72h)后,较相应质量浓度或时间的BSA组和空白对照组均明显升高(P<0.05);抗RAGE抗体干预后能够部分抑制AGE-BSA诱导CTGF及FN的表达,而人IgG没有这种作用。结论:AGEs可能通过RAGE诱导CTGF及FN的表达上调,是糖尿病肾病肾脏纤维化的可能机制。AIM： To investigate the effects of advanced glycosylation end products （AGEs） modified bovine serum albumin （ AGE - BSA） on the expression of connective tissue growth factor （CTGF） and fibronectin （FN） in human renal mesangial ceils （HRMCs）. METHODS： HRMCs were cultured in vitro with medium containing different doses of AGE- BSA or BSA （50, 100, 200, 400 mg/L） for 48 h, or with AGE- BSA （200 mg/L） for different times （12, 24, 48, 72 h）. Western blotting was applied to estimate the protein level of receptor for advanced glycosylation end products （RAGE）. The mRNA expression of CTGF and FN were analyzed by semi - quantitative reverse transcription - polyrnerase chain reaction （RT- PCR） after treatment with AGE -BSA or BSA. RESULTS： The low level of RAGE expression was observed in the HRMCs. The protein level of RAGE was up - regulated in the HRMCs treated with AGE - BSA. The mRNA expression of CTGF and FN significantly enhanced by incubation of AGE - BSA in a time - and dose - dependent manners. The effects of AGE - BSA - induced up - regulation of CTGF and FN in mRNA level were significantly blocked by the neutralizing antibodies to RAGE, while the mRNA expression of CTGF and FN remained nearly unchanged after cultured with human lgG. CONCLUSION： The expression of CTGF and FN in HRMCs is induced by AGE - BSA through RAGE, which may have potential effects on the pathogenesis of diabetic nephropathy.

关 键 词：糖基化终产物 高级 肾小球系膜细胞 受体 结缔组织生长因子 纤维蛋白类 

分 类 号：R587.1[医药卫生—内分泌]