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色素上皮衍生因子抑制糖基化终产物介导人肾小球系膜细胞糖基化终产物受体表达的研究

来自:中国糖尿病杂志  编辑: 盛霞 秦淑兰 朱艳 沈浩 张喜婷|点击数:|2014-12-16

  ·糖尿病基础研究·

  色素上皮衍生因子抑制糖基化终产物介导人肾小球系膜细胞糖基化终产物受体表达的研究

  盛霞 秦淑兰 朱艳 沈浩 张喜婷

  【摘要】 目的 观察色素上皮衍生因子(PEDF)、晚期糖基化终产物受体(RAGE)的表达及重组PEDF对RAGE表达的抑制作用,探讨PEDF与DN的关系及对DN的保护作用。 方法 采用糖化小牛血清白蛋白(AGE-BSA)体外诱导HRMCs,Western bloting及RT-PCR法分别检测RAGE、PEDF蛋白和mRNA表达。 结果 (1)AGE-BSA(100~400 mg/L)呈浓度梯度减少HRMCs PEDF表达(P<0.01),升高RAGE表达(P<0.01);(2)重组PEDF蛋白(5~40 nmol/L)呈浓度依赖性抑制AGE-BSA介导RAGE蛋白在HRMCs的表达(P<0.05)。 结论 AGEs通过降低PEDF表达,增加RAGE表达参与DN的发生,PEDF可能通过抑制AGE-RAGE轴对DN发挥着保护作用。

  【关键词】 色素上皮衍生因子;糖尿病肾病;晚期糖基化终产物;受体;肾小球系膜细胞

  【Abstract】 To observe the effects of advanced glycation end-products (AGEs) on the expression of pigment epithelium-derived factor (PEDF) and on the expression of receptor of AGEs (RAGE) in the cultured human renal mesangial cells (HRMCs) and the effect of PEDF on diabetic nephropathy. Methods HRMCs were treated in vitro with AGE-bovine serum albumin (AGE-BSA) in the absense or presense of recombinant PEDF. Protein and mRNA of RAGE and PEDF were detected by Western blotting and RT-PCR method respectively. Results (1) AGE-BSA(100~400 mg/L) significantly increased RAGE expression and reduced the expression of PEDF in HRMCs(P<0.01). (2) Recombinant PEDF (5~40 nmol/L) inhibited AGEs-induced expression increase of RAGE in a dose-dependence manner. Conclution AGEs increase RAGE expression and reduce PEDF expression in HRMCs , which may contribute to DN;PEDF inhibits AGEs-induced expression of RAGE, which could be a new therapeutic target in diabetic nephropathy.

  【Key Words】 Pigment epithelium-derived factor; Glycation end products, advanced; Receptor; Diabetic nephropathy; Renal mesangial cell

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