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

Abstract

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.

Exosomal MicroRNAs as Potential Biomarkers of Hepatic Injury and Kidney Disease in Glycogen Storage Disease Type Ia Patients

“…In particular, these microRNAs have been associated with diabetic kidney disease, one of the major microvascular complications in patients with type 1 or type 2 diabetes, which represents the primary cause of end-stage renal disease. miR-483-5p has diagnostic value in diabetic nephropathy and can protect human proximal renal tubular cells from the apoptosis and inflammation induced by high glucose [ 31 ]. The serum levels of miR-122-5p correlate with the albuminuria, glomerular filtration rate, blood glucose and lipid profiles in patients with diabetic kidney disease and type 2 diabetes mellitus [ 32 ].…”

MiR-218 promotes oxidative stress and inflammatory response by inhibiting SPRED2-mediated autophagy in HG-induced HK-2 cells

“…Many studies used similar in vitro models to investigate DN. [22][23][24] These findings might provide new promising therapeutic strategies for DN.…”

Expression profile of urinary exosomal miRNAs in patients with diabetic kidney disease and their associated with kidney damage

“…Liu et al con rmed that circulating miR-483-5p was signi cantly downregulated in DKD patients, and could distinguish DKD from T2DM patients. Such, it is possible that circulating miR-483-5p would become a noninvasive biomarker for diagnosis of DKD [31,32] . Su et al analyzed miRNA expression pro les in kidney tissues from DKD patients through miRNA microarray, and found that miR-483-5p was observably downregulated [33] .…”