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
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Department of Nephrology, Weifang City Traditional Chinese Medical Hospital, Weifang, Shandong Province, China
Submission date: 2019-06-03
Final revision date: 2019-08-22
Acceptance date: 2019-09-06
Online publication date: 2019-11-11
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).

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. In vitro 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, p < 0.001; AUC = 0.822, p < 0.001 or AUC = 0.922, p < 0.001) with DN was better than in type 1 diabetes mellitus patients (AUC = 0.805, p < 0.001; AUC = 0.722, p < 0.001 or AUC = 0.865, p < 0.001) with DN.

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