BMP-7对高糖诱导近端肾小管上皮细胞外基质及NF-κΒ表达的影响  

The role of bone morphogenetic protein-7 (BMP-7) in inducing expression of extracellular matrix and nuclear factor-κΒ in proximal tublar epithelial cells by high glucose level

作　　者：王代红[1] 刘理[2] 袁发焕[1] 张耀全[1] 

机构地区：[1]第三军医大学新桥医院肾内科,重庆400037 [2]第三军医大学新桥医院内分泌科,重庆400037

出　　处：《解放军医学杂志》2006年第8期755-757,共3页Medical Journal of Chinese People's Liberation Army

摘　　要：目的探讨骨形态发生蛋白7(BMP-7)对高糖诱导近端肾小管上皮细胞(HKc)表达细胞外基质及核转录因子-κΒ(NF-κΒ)的干预作用。方法采用人近端肾小管HKc细胞株,将细胞分为正常对照组(NG,5·5mmol/L葡萄糖)、高糖组(HG,25mmol/L葡萄糖)、HG+100ng/mlBMP-7组、NG+100ng/mlBMP-7组、高渗组(HM,25mmol/L甘露醇)。应用免疫细胞化学和ELISA技术检测细胞Ⅳ型胶原(ColⅣ)、纤维连接蛋白(FN)表达,用凝胶电泳迁移率竞争试验(EMSA)检测NF-κΒ的表达。结果高糖作用下NF-κΒ活性和Ⅳ型胶原、纤维连接蛋白表达显著增高,加入100ng/mlBMP-7后可显著抑制NF-κΒ活性及Ⅳ型胶原、纤维连接蛋白的表达。结论BMP-7可能通过抑制NF-κΒ活性而从转录水平抑制高糖诱导的近端小管细胞细胞外基质的过度表达。Objective To investigate the effect of bone morphogenetic protein-7 （BMP-7） on high glucose-induced expression of fibronectin （FN） and collagen Ⅳ （Col Ⅳ） and activity of nuclear factor-κB （NF-κB） in human renal tubular epithelial cells. Methods Human renal tubular epithelial cells （HKCs） in culture were divided into 5 groups： normal glucose group with 5. 5 mmol/L glucose （NG）, high glucose group with 25 mmol/L D-glucose （HG）, HG＋100 ng/ml BMP-7, NG＋100 ng/ml BMP-7 and high osmolality group with 25 mmol/L mannitol （HM）. Thus HKCs were respectively stimulated with high glucose, high mannitol and BMP-7. Expression of collagen Ⅳ and fibronectin was determined by immunocytochemistry and enzyme linked immunosorbent assay （ELISA） and activity of nuclear factor-κB was assessed with electrophoretic mobility shift assay （EMSA）. Results Compared with normal glucose, high glucose concentration up-regulated expression of FN and Col Ⅳ and activity of NF-κB （P〈0. 05）, but mannitol with the same osmolality had no significant effects （P〉0. 05）. With addition of BMP-7 in a concentration of 100ng/ml to the high glucose medium, expression of Col Ⅳ and FN was suppressed, and the activity of nuclear factor-κB was inhibited in human tubular epithelial cells （P〈0. 05）. Conclusions BMP-7 may inhibit the expression of Col Ⅳ and FN in proximal tubular epithelial cells in response to high blood glucose via its inhibitory effect on activity of NF-κB, and it may be one of the potential effective measures to prevent diabetic nephropathy.

关 键 词：糖尿病肾病 骨形态发生蛋白质类 胶原Ⅳ型 纤连蛋白类 NF-κB 

分 类 号：R587.24[医药卫生—内分泌]