Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. The aim of our study was to investigate the potential mechanism in DN progression. SV40 mesangial cells (MES)13 cells were exposed to high concentration of glucose (HG: 30 mmol/L) for 48 hours to establish a DN cell model in vitro. Bioinformatic software StarBase was adopted to establish the long noncoding RNA (lncRNA)-microRNA–messenger RNA axis. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay were performed to verify intermolecular interaction. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was overexpressed in the serum of patients with DN. HG time-dependently upregulated NEAT1 levels, and HG promotes cell proliferation, oxidative stress, inflammation, and fibrosis and suppressed cell apoptosis in SV40 MES13 cells partly through upregulating NEAT1. NEAT1 functioned as a molecular sponge of miR-423-5p, and NEAT1 silencing-mediated effects were partly overturned by miR-423-5p interference in HG-induced SV40 MES13 cells. Glioma pathogenesis related-2 (GLIPR2) was a target of miR-423-5p. GLIPR2 overexpression in normal concentration of glucose (NG)-induced SV40 MES13 cells partly simulated HG-induced effects. GLIPR2 overexpression partly reversed NEAT1 interference–induced effects in HG-induced SV40 MES13 cells. LncRNA NEAT1 contributed to HG-induced DN progression through the miR-423-5p/GLIPR2 axis in vitro. NEAT1/miR-423-5p/GLIPR2 axis might be a potential target for DN treatment.

糖尿病肾病（DN）是糖尿病的严重微血管并发症。我们研究的目的是研究 DN 进展的潜在机制。SV40系膜细胞（MES）13细胞暴露于高浓度葡萄糖（HG：30 mmol/L）48小时，建立体外DN细胞模型。采用生物信息学软件 StarBase 建立长链非编码 RNA（lncRNA）-microRNA-信使 RNA 轴。进行双荧光素酶报告基因测定、RNA 免疫沉淀测定和 RNA 下拉测定以验证分子间相互作用。LncRNA 核副啄木鸟组装转录本 1 (NEAT1) 在 DN 患者的血清中过表达。HG 时间依赖性上调 NEAT1 水平，并且 HG 促进细胞增殖、氧化应激、炎症、SV40 MES13 细胞的纤维化和抑制细胞凋亡部分是通过上调 NEAT1 来实现的。NEAT1 充当 miR-423-5p 的分子海绵，并且 NEAT1 沉默介导的作用被 HG 诱导的 SV40 MES13 细胞中的 miR-423-5p 干扰部分推翻。胶质瘤发病机制相关-2（GLIPR2 ) 是 miR-423-5p 的靶标。GLIPR2在正常浓度的葡萄糖 (NG) 诱导的 SV40 MES13 细胞中过表达部分模拟了 HG 诱导的效应。GLIPR2过表达部分逆转了 HG 诱导的 SV40 MES13 细胞中 NEAT1 干扰诱导的作用。LncRNA NEAT1 在体外通过 miR-423-5p/ GLIPR2轴促进 HG 诱导的 DN 进展。NEAT1/miR-423-5p/ GLIPR2轴可能是 DN 治疗的潜在靶点。