MiR-372-3p is a Potential Diagnostic Factor for Diabetic Nephropathy and Modulates High Glucose-induced Glomerular Endothelial Cell Dysfunction Via Targeting Fibroblast Growth Factor-16

Introduction: Previous studies have reported that microRNAs are implicated in the pathogenesis of diabetic nephropathy (DN). In this study, the underlying molecular mechanisms and diagnostic significance of miR-372-3p were investigated in the process of DN.

Material And Methods: Cell proliferation and apoptosis were measured using MTT and Annexin V-FITC double staining, respectively. RT-qPCR and western blotting were used to measure the expression levels of mRNA and protein. The diagnostic power of miR-372-3p in plasma for DN was evaluated using the receiver operating characteristics (ROC) curves and the area under the ROC curves (AUC).

Results: miR microarray analysis revealed that 126 miRs were significantly differentially expressed in response to high glucose stimulation. Among these miRs, high glucose stimulated miR-372-3p expression at the highest level. experimental measurements showed that knockdown of miR-372-3p showed the ability to reverse high glucose-induced glomerular endothelial cell apoptosis and impairment of eNOS/NO bioactivity. Mechanistic analysis revealed that fibroblast growth factor-16 (FGF-16) as a direct of miR-372-3p protected against high glucose-induced glomerular endothelial cell dysfunction. ROC analysis revealed that the diagnostic value of miR-372-3p, miR-15a or miR-372-3p combined with miR-15a in type 2 diabetes mellitus patients (AUC = 0.841, < 0.001; AUC = 0.822, < 0.001 or AUC = 0.922, < 0.001) with DN was better than in type 1 diabetes mellitus patients (AUC = 0.805, < 0.001; AUC = 0.722, < 0.001 or AUC = 0.865, < 0.001) with DN.

Conclusions: miR-372-3p might be a valuable therapeutic target and diagnostic marker for patients with DN.