KIDNEY INT:DNA甲基转移酶1治疗糖尿病肾病足细胞损伤的新靶点!

2017-03-20 xing.T MedSci原创

因此,抑制DNA甲基化可能是治疗糖尿病肾病的一条新治疗途径。因此,SP1/NFκB p65-DNMT1通路可能作为治疗靶点来预防糖尿病肾病足细胞损伤。

DNA甲基化是否可以促进糖尿病肾病的发生发展,尤其是对足细胞完整性的影响,尚不明确。近日,肾脏病领域权威杂志kidney international上发表了一篇研究文章,研究人员发现用DNA甲基化抑制剂治疗糖尿病模型的db/db小鼠可以显著降低它们尿液中的蛋白含量。

此外,研究人员还发现db/db小鼠经DNA甲基化抑制剂治疗后,肾小球肥大、肾小球系膜扩张与足细胞损伤均有所减轻。在糖尿病状态下,体内和体外足细胞中DNA甲基转移酶1(DNMT1)、核转录因子Sp1和核因子-κB(NF-κB)-p65的表达显著增加。增加的DNMT1蛋白表达在采用5-氮胞苷或5-氮-2’-脱氧胞苷处理以及DNMT1敲除后可以显著降低,伴随着减少的足细胞裂孔隔膜蛋白表达恢复,产生高甲基化和改善足细胞活力。

进一步的研究发现,在高糖培养的足细胞细胞核中,Sp1和NFκB-p65的相互作用增强,并且Sp1结合到DNMT1基因启动子区。Sp1/NFκB-p65复合体参与DNMT1的调节可以通过观察采用光辉霉素A或siRNA沉默Sp1后可以降低DNMT1蛋白水平来证实。荧光素酶报告基因实验进一步表明DNMT1是Sp1的直接目标。

因此,抑制DNA甲基化可能是治疗糖尿病肾病的一条新治疗途径。因此,SP1/NFκB p65-DNMT1通路可能作为治疗靶点来预防糖尿病肾病足细胞损伤。

原始出处:


Li Zhang,et al. DNA methyltransferase 1 may be a therapy target for attenuating diabetic nephropathy and podocyte injury.kidney-international.2017. http://dx.doi.org/10.1016/j.kint.2017.01.010

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    2017-06-18 laoli

    谢谢了,学习了!

    0

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    2017-03-22 lsndxfj
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    2017-03-22 gwc389

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