LncRNA NEAT1 Accelerates the Proliferation, Oxidative Stress, Inflammation, and Fibrosis and Suppresses the Apoptosis Through the miR-423-5p/GLIPR2 Axis in Diabetic Nephropathy

Abstract

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.