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

• Published in: Pharmaceutical research 2023-04, Vol.40 (4), p.817-832
• Main Authors: Zapała, Barbara, Kamińska, Agnieszka, Piwowar, Monika, Paziewska, Agnieszka, Gala-Błądzińska, Agnieszka, Stępień, Ewa Ł.
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Chronic kidney failure; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Diabetic Nephropathies; Extracellular vesicles; Extracellular Vesicles - metabolism; Genetic transcription; Genomes; Genomics; Health aspects; Humans; Inflammation; Kidney diseases; Medical Law; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Original; Original Research Article; Pharmacology/Toxicology; Pharmacy; Renal Insufficiency, Chronic; Reverse transcription; RNA sequencing; Size distribution; Type 2 diabetes
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-023-03481-5

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.