Endocrine Abstracts

Background and aims: Diabetic kidney disease (DKD) is a common microvascular complication that affects 40% of patients with diabetes mellitus (DM). Emerging evidence suggests a role for microRNAs (miRNAs) in the development of DKD. In this context, miR-15a-5p and miR-30e-5p have been shown to regulate the expression of the uncoupling protein 2, a mitochondrial protein that decreases reactive oxygen species (ROS) formation by mitochondria. Since ROS overproduction is a key contributor to the pathogenesis of DKD, dysregulation of these miRNAs may be involved in DKD pathogenesis. Thus, the aims of this study were to compare miR-15a-5p and miR-30e-5p expressions in plasma and urine of type 1 DM (T1DM) patients with DKD (cases) or without this complication (controls) and to perform bioinformatics analyses to investigate their putative targets and biological pathways under their regulation.

Methods: MiR-15a-5p and miR-30e-5p expressions were analyzed in plasma and urine of 17 T1DM controls and 23 DKD cases (12 with moderate DKD and 11 with severe DKD) using real-time PCR. DKD was classified following the Kidney Disease Improving Global Outcomes guidelines, using both urinary albumin excretion (UAE) levels and estimated glomerular filtration rate (eGFR). Bioinformatics analyses were performed using the Cytoscape software.

Results: MiR-30e-5p expression was downregulated in plasma of patients with moderate or severe DKD compared to T1DM controls [severe DKD: 0.53 median (0.25–0.84, 25th–75th percentiles), moderate DKD: 0.25 (0.08–0.82), and T1DM controls: 2.42 (0.51–4.33) n fold changes, P=0.003]. In urine samples, miR-30e-5p expression was only downregulated in severe DKD group compared to the other groups [severe DKD: 0.34 (0.05 – 0.85), moderate DKD: 3.92 (0.23 – 9.66), and T1DM controls: 2.96 (0.99 – 5.97), P=0.017]. No difference was found in miR-15a-5p expression among groups. MiR-15a-5p and miR-30e-5p expressions showed significant negative correlations with UAE (r=−0.459, P=0.016 and r=−0.617, P=0.0001, respectively) and HbA1c levels (r=−0.432, P=0.009 and r=−0.435, P=0.004, respectively). No correlation was found between these miRNAs and eGFR or creatinine levels. Bioinformatics analyses indicate that 2197 genes are putative targets of miR-15a-5p and 2208 of miR-30e-5p, being 314 of these genes modulated by both miRNAs. Moreover, these genes participate in pathways related to angiogenesis, apoptosis, cell differentiation, oxidative stress, and hypoxia.

Conclusions: MiR-30e-5p seems to be downregulated in plasma and urine of patients with DKD. Bioinformatics analyses suggested that miR-15a-5p and miR-30e-5p regulate genes involved in key mechanisms related to DKD pathogenesis.