MRTF-A通过NF-κB参与AGEs诱导肾小球系膜细胞中FN、ICAM-1的表达  

MRTF-A mediates FN and ICAM-1 expressions by NF-κB pathway in AGEs-induced GMCs

作　　者：陈秋红[1] 陈志泉[1] 黄佳妮[1] 黄河清[1,2] 

机构地区：[1]中山大学药学院 [2]广东省疾病模式动物工程技术研究中心,广东广州510006

出　　处：《中国药理学通报》2017年第4期572-577,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81373457;81573477);教育部博士点基金(No 20130171110097);广东省科技计划项目(No 2015B090903063)

摘　　要：目的该研究观察在糖基化终末产物(AGEs)诱导大鼠肾小球系膜细胞(GMCs)中,心肌素相关转录因子MRTFA的变化及其对细胞黏附分子(ICAM-1)及纤维连接蛋白(FN)的影响,探讨MRTF-A是否通过影响NF-κB信号通路参与糖尿病肾病。方法 AGEs条件下,抑制剂CCG-1423抑制MRTF-A,或对MRTF-A进行过表达,干扰处理,通过Western blot检测MRTF-A、ICAM-1和FN的蛋白水平变化及p65在细胞核内的水平。结果在AGEs诱导的GMCs中,MRTF-A的蛋白表达增加;干扰或抑制MRTF-A能够下调AGEs诱导的FN和ICAM-1的蛋白表达及p65入核水平;而过表达MRTF-A则进一步上调FN和ICAM-1的蛋白表达及p65入核水平。结论 AGEs能够上调GMCs中MRTF-A的表达,且MRTF-A通过影响NF-κB信号通路参与介导了AGEs诱导的FN和ICAM-1的蛋白表达。Aim To observe the expression of MRTF-A in rat glomerular mesangial cells（ GMCs） induced by advanced glycation end products（ AGEs） and its effect on ICAM-1 and FN;to explore whether MRTF-A is involved in the process of diabetic nephropathy by affecting NF-κB pathway.Methods Under the condition of AGEs,CCG-1423 and anti-MRTF-A small interfering RNA were used to knock down MRTF-A and MRTF-A plasmid was used to activatt MRTF-A,The expression level of MRTF-A,ICAM-1,FN and p65 in nucleus were detected by Western blot.Results The protein expressions of MRTF-A was increased in AGEs-induced GMCs.The expressions of FN and ICAM-1 and p65 in nucleus were downregulated by knocking down MRTF-A.However,the expressions of FN,ICAM-1and p65 in nucleus were upregulated by overexpressing MRTF-A.Conclusions AGEs can upregulate the expression of MRTF-A in GMCs,and MRTF-A mediates the protein expressions of FN and ICAM-1 by affecting NF-κB signaling pathway in AGEs-induced GMCs.

关 键 词：糖尿病肾病 肾小球系膜细胞 AGES MRTF-A P65 FN ICAM-1 

分 类 号：R322.61[医药卫生—人体解剖和组织胚胎学] R341[医药卫生—基础医学]