色素上皮衍生因子对高糖诱导人肾小球系膜细胞p38丝裂原活化蛋白激酶-cAMP反应元件结合蛋白通路及纤连蛋白的影响  

Effect of pigment epithelium-derived factor on p38MAPK-CREB pathway and fibronectin in high glucose cultured human mesangial cells

作　　者：高兰[1] 李竞[1] 高凌[1] 陈红敏[1] 洪练[1] 

机构地区：[1]武汉大学人民医院内分泌科,430060

出　　处：《中华肾脏病杂志》2012年第3期212-216,共5页Chinese Journal of Nephrology

摘　　要：目的探讨色素上皮衍生因子（PEDF）对高糖条件下人肾小球系膜细胞（HMC）p38丝裂原活化蛋白激酶（p38MAPK）、cAMP反应元件结合蛋白（CREB）及细胞外基质成分纤连蛋白（FN）的影响。方法体外予正常糖（5．6mmol／L）、甘露醇（24．4mmol／L）、高糖（30mmol／L）、高糖＋PEDF（30mmol／L葡萄糖＋10nmol／L、40nmol／L、100nmol／LPEDF）培养基培养HMC24h，观察p38MAPK、CREB活性（Western印迹）及FNmRNA（RT—PCR）和蛋白（ELISA）的变化。结果与正常糖及甘露醇组相比，高糖组p-p38MAPK、p-CREB、FN的表达均显著升高（均P〈0．01）；与高糖组相比，PEDF干预组上述指标的表达均显著下降（均P〈0．05）。结论PEDF可能通讨D38MAPK．CREB诵足各抑制糖尿病肾病的纤维化．Objective To investigate the effect of pigment epithelium- derived factor （PEDF） on p38MAPK-CREB pathway and the expression of fibronectin （FN） in human mesangial cells （HMCs） cultured with high glucose. Methods HMCs were treated with different concentrations of glucose and the osmotic control respectively in the presence or absence of PEDF for 24 h： normal glucose （5.6 mmol/L）, 24.4 mmol/L mannitol, high glucose （30 mmol/L）, high glucose＋PEDF（30 mmol/L glucose with 10 nmol/L PEDF, 40 nmol/L PEDF or 100 nmol/L PEDF）. After samples were collected, the expression of phospho-p38MAPK （p-p38） and p-CREB was assessed by Western blotting, while FN mRNA and protein expression was assessed with RT-PCR and ELISA respectively. Results In contrast to normal glucose and mannitol treatments, the expression of p-p38MAPK, p-CREB and FN increased significantly in high glucose group （all P〈 0.01）. However, PEDF abolished the up-regulation of p-p38MAPK, p-CREB and FN induced by high glucose （all P〈0.05）. Conclusion PEDF may inhibit fibrosis through P38MAPK-CREB pathway in diabetic nephropathy.

关 键 词：肾小球系膜细胞 P38丝裂原活化蛋白激酶类 CAMP反应元件结合蛋白质 纤连蛋白类 色素上皮衍生因子 

分 类 号：R363[医药卫生—病理学]