Abstract
IntroductionDiabetic kidney disease (DKD) is a common microvascular complication that affects 40% of patients with diabetes mellitus (DM). Emerging evidence suggests a role for several 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 (UCP2), a mitochondrial protein that decreases reactive oxygen species (ROS) formation by the mitochondria. Since ROS overproduction is a key contributor to the pathogenesis of DKD, dysregulation of these two miRNAs could be involved in DKD pathogenesis. Thus, the aim of this study was to compare the expressions of miR-15a-5p and miR-30e-5p in type 1 DM (T1DM) patients with DKD (cases) and without this complication (controls), and to perform bioinformatics analyses to investigate their putative targets and biological pathways under their regulation.MethodsMiR-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 qPCR. Bioinformatics analyses were performed in Cytoscape software.ResultsMiR-30e-5p expression was downregulated in plasma of patients with moderate and severe DKD compared to T1DM controls. Moreover, this miRNA was also downregulated in urine of patients with severe DKD compared to the other groups. No difference was found in miR-15a-5p expression between groups. Bioinformatics analyses indicated that miR-30e-5p and miR-15a-5p regulate various genes that participate in pathways related to angiogenesis, apoptosis, cell differentiation, oxidative stress, and hypoxia.ConclusionMiR-30e-5p seems to be downregulated in plasma and urine of patients with DKD.
Highlights
Diabetic kidney disease (DKD) is a common microvascular complication that affects 40% of patients with diabetes mellitus (DM)
MiR-30e-5p expression was downregulated in plasma of patients with moderate and severe DKD compared to type 1 DM (T1DM) controls
Bioinformatics analyses indicated that miR-30e-5p and miR-15a-5p regulate various genes that participate in pathways related to angiogenesis, apoptosis, cell differentiation, oxidative stress, and hypoxia
Summary
Diabetic kidney disease (DKD) is a common microvascular complication that affects 40% of patients with diabetes mellitus (DM). Emerging evidence suggests a role for several microRNAs (miRNAs) in the development of DKD. In this context, miR15a-5p and miR-30e-5p have been shown to regulate the expression of the uncoupling protein 2 (UCP2), a mitochondrial protein that decreases reactive oxygen species (ROS) formation by the mitochondria. Regarding epigenetic factors, emerging evidence has suggested an important role of microRNAs (miRNAs) in the pathogenesis of DKD (Kato and Natarajan, 2015; Wanner and Bechtel-Walz, 2017; Assmann et al, 2018a,b). MiRNAs are small (∼=21–23 nucleotides) non-coding RNAs that regulate gene expression of 60% of protein coding genes (Assmann et al, 2017); regulating many cellular functions and influencing the development and progression of a number of diseases (Kato and Natarajan, 2015; Assmann et al, 2017, 2018b)
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