Department of Nephrology, the Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006, P.R. China.
Department of Medicine, the George Washington University, Washington, DC20052, USA.
Sci Rep. 2017 Jun 27;7(1):4261. doi: 10.1038/s41598-017-00686-8.
Diabetic kidney disease (DKD) is a serious complication of hyperglycemia. Currently, there is no effective therapeutic intervention for DKD. In this study, we sought to provide a set of gene profile in diabetic kidneys. We identified 338 genes altered in diabetes-induced DKD glomeruli, and PLK2 exhibited the most dramatic change. Gene set enrichment analysis (GSEA) indicated multiple signaling pathways are involved DKD pathogenesis. Here, we investigated whether PLK2 contributes to podocyte dysfunction, a characteristic change in the development of DKD. High D-glucose (HDG) significantly increased PLK2 expression in mouse podocytes. Suppressing PLK2 attenuated HDG-induced apoptosis and inflammatory responses both in vitro and in vivo. NAC, an antioxidant reagent, rescued HDG and PLK2 overexpression-induced kidney injuries. In summary, we demonstrated that silencing PLK2 attenuates HDG-induced podocyte apoptosis and inflammation, which may serve as a future therapeutic target in DKD.
糖尿病肾病（DKD）是一种严重的高血糖并发症。目前，对于 DKD 还没有有效的治疗干预手段。在本研究中，我们试图提供一套在糖尿病诱导的 DKD 肾小球中改变的基因谱。我们鉴定出 338 个在糖尿病诱导的 DKD 肾小球中改变的基因，其中 PLK2 的变化最为显著。基因集富集分析（GSEA）表明，多个信号通路参与了 DKD 的发病机制。在这里，我们研究了 PLK2 是否有助于足细胞功能障碍，这是 DKD 发展的一个特征性变化。高葡萄糖（HDG）显著增加了小鼠足细胞中 PLK2 的表达。在体外和体内，抑制 PLK2 均可减轻 HDG 诱导的细胞凋亡和炎症反应。NAC，一种抗氧化剂试剂，可挽救 HDG 和 PLK2 过表达诱导的肾脏损伤。综上所述，我们证明了沉默 PLK2 可减轻 HDG 诱导的足细胞凋亡和炎症，这可能成为 DKD 的未来治疗靶点。
