Enrichment of RedoxifibromiR miR-21-5p in Plasma Exosomes of Hypertensive Patients with Renal Injury

Fecha de publicación: 01/01/2025 Fecha Ahead of Print: 12/01/2025

Grupos y Plataformas de I+D+i

Grupo de Estudio de Riesgo Cardiometabólico y Renal

Established Researcher

Raquel Cortés Vergaz
Grupo de Investigación sobre Riesgo Cardiometabólico y Diabetes

Leading Researcher

Sergio Martinez Hervas

Abstract

Several microRNAs (miRNAs) emerged as powerful regulators of fibrotic processes, "fibromiRs", and can also influence the expression of genes responsible for the generation of reactive oxygen species, "redoximiRs". We aimed to investigate whether plasma exosomes from hypertensive and diabetes patients are enriched in fibromiRs and redoximiRs using deep sequencing technology and their association with relevant signalling pathways implicated in oxidative stress and fibrogenesis by GO terms and KEGG pathways. RNA-Seq analysis from P-EXO identified 31 differentially expressed (DE) miRNAs in patients compared to controls, of which 77% are biofluid specific. The majority of the exosomal DE miRNAs were identified as fibromiRs (55%) or redoximiRs (26%). One of the most representative miRNAs identified was miR-21-5p, of which levels in P-EXO were increased by 3.83-fold change (p < 0.0001) in hypertensive patients with albuminuria and were highly associated (r Spearman = 0.64, p < 0.0001). In addition, P-EXO miR-21-5p had a high accuracy in discriminating renal damage (AUC = 0.82, p < 0.0001). Bioinformatic analysis revealed that miR-21-5p regulates key pathways in the context of organ fibrosis, such as chemokine, Ras, and MAPK signalling. Additionally, in vitro studies showed an increase in P-EXO miR-21-5p levels after TGF-beta 1 damage and oxidative stress. This novel study found an enrichment of fibromiRs and redoximiRs in P-EXO from hypertensive/diabetic patients with renal dysfunction. miR-21-5p, such as a RedoxifibromiR, has a significant accuracy for discriminating renal damage and is closely related with relevant signalling pathways implicated in fibrogenesis in podocytes.