miRNA Signature of Urine Extracellular Vesicles Shows the Involvement of Inflammatory and Apoptotic Processes in Diabetic Chronic Kidney Disease

Abstract

Background The aim of this study was to investigate the role of urine-derived extracellular vesicles (uEVs) in diabetic kidney disease (DKD) in patients diagnosed with type 2 diabetes mellitus (T2DM). Methods UEVs were characterized by size distribution and microRNA content by next-generation small RNA sequencing and quantitative reverse transcription PCR. Results A subset of sixteen miRNAs enriched in T2DM patients with DKD, including hsa-miR-514a-5p, hsa-miR‑451a, hsa-miR-126-3p, hsa-miR-214, or hsa-miR‑503 was identified. Eight miRNAs as hsa-miR-21-3p, hsa-miR-4792, hsa-miR‑375, hsa-miR-1268a, hsa-miR-501-5p, or hsa-miR-582 were downregulated. Prediction of potential target genes and pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) confirmed possible functions related to cellular processes such as apoptosis, inflammation, and tissue remodeling, that promote diabetic complications, such as DKD. Among them, hsa-miR-375, hsa-miR-503, and hsa-miR-451a make important contribution. Additionally, downregulated hsa-miR-582-5p has not been reported so far in any diabetes-related pathways. Conclusions This study revealed the most significant miRNAs in uEVs of patients with T2DM. However, as this is a bioinformatic prediction that we performed based on the putative targets of the identified miRNAs. Thus, further in vitro functional studies are needed to confirm our findings. Knowing the fact that EVs are crucial in transferring miRNAs, there is a great need toto discover their involvement in the pathomechanism of T2DM-related kidney disease.

A Systematic Review and Meta-Analysis of microRNA Profiling Studies in Chronic Kidney Diseases

“…In detail, ten articles reported two to three different disease types separately [ 25 , 26 , 30 , 33 , 34 , 36 , 38 , 39 , 43 , 53 ]. Of the total 55 individual results, 13 focused solely on diabetic nephropathy (DN) [ 24 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ], 10 focused on IgA nephropathy (IgAN) [ 34 , 39 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 54 ], and 4 did not specify the form of CKD [ 23 , 52 , 53 , 55 ]. The rest of the studies included lupus nephritis (LN) or post-streptococcal glomerulonephritis (PSGN) (n = 7) [ 26 , 27 , 28 , 29 , 33 , 51 , 56 ], focal segmental glomerulosclerosis (FSGS) (n = 5) [ 25 , 30 , 38 , 39 , 57 ] or minimal change disease (MCD) (n = 5) [ 25 ,…”

Genetic and Transcriptomic Background of Oxidative Stress and Antioxidative Therapies in Late Complications of Type 2 Diabetes Mellitus: A Systematic Review

“…In another pilot study that included eight T2DM patients with DKD and eight controls without T2DM, EVs were isolated from the urine, and their miRNA content was sequenced by NGS. The bioinformatic analysis of the most differentially expressed miRNA predicted the involvement of molecular processes related to inflammation and apoptosis in the development of DKD [ 103 ].…”

Tp47-Induced Monocyte-Derived Microvesicles Promote the Adherence of THP-1 Cells to Human Umbilical Vein Endothelial Cells via an ERK1/2–NF-κB Signaling Cascade

“…Tp47 induces the adherence of THP-1 cells to human dermal vascular smooth muscle cells by increasing adhesion-associated cytokine production ( 10 ). Microvesicles belong to a group of heterogeneous membrane-coated vesicles that can function as signaling components in inflammatory processes ( 18 ). However, it is unclear whether microvesicles are involved and mediate the interaction of immunocytes with vascular cells to contribute to vascular inflammation.…”