miRNA-483–5p Targets HDCA4 to Regulate Renal Tubular Damage in Diabetic Nephropathy

摘要

This study was designed to evaluate the diagnostic value of miR-483–5p in diabetic nephropathy (DN), and its effect and mechanism on apoptosis and inflammation of human proximal renal tubular cells (HK2) induced by high glucose (HG). Thirty healthy controls, 30 types 2 diabetes mellitus (T2DM) patients, and 28 DN patients were enrolled. miR-483–5p mRNA levels in serum were analyzed by RT-qPCR assays. The receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of miR-483–5p in DN. HK2 cells were induced by HG to establish an in vitro study model. CCK-8 and flow cytometry was used to detect cell viability, apoptosis, and reactive oxygen species (ROS) generation. Inflammation levels were measured by ELISA. Luciferase reporter assay was used to detect target genes of miR-483–5p. miR-483–5p was decreased in DN patients. The decreased level of miR-483–5p was positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with proteinuria. miR-483–5p can significantly distinguish DN patients from healthy controls and T2DM and has a high diagnostic value. miR-483–5p decreased in HK2 cells induced by HG, and overexpression of miR-483–5p reversed HG-induced decreased cell activity, increased apoptosis, ROS production, and inflammation. Histone deacetylase 4 (HDCA4) was markedly increased in DN patients and HG-induced HK2 cells. miR-483–5p directly targeted HDCA4, and increasing miR-483–5p inhibited HDCA4 increased in HG-induced HK2. In conclusion, the results indicate that reduction of miR-483–5p has a high diagnostic value in DN, and overexpression of miR-483–5p has a certain protective effect on HK2 cells induced by HG by targeting HDCA4.