Repositorio
Institucional

Ortega, Ana

Flores-Chova, Ana

Martinez-Arroyo, Olga

Riffo-Campos, Angela L. L.

Forner, Maria J. J.

Cortes, Raquel

Plasma Exosomal Non-Coding RNA Profile Associated with Renal Damage Reveals Potential Therapeutic Targets in Lupus Nephritis

MDPI

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

en

Despite considerable progress in our understanding of systemic lupus erythematosus (SLE) pathophysiology, patient diagnosis is often deficient and late, and this has an impact on disease progression. The aim of this study was to analyze non-coding RNA (ncRNA) packaged into exosomes by next-generation sequencing to assess the molecular profile associated with renal damage, one of the most serious complications of SLE, to identify new potential targets to improve disease diagnosis and management using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The plasma exosomes had a specific ncRNA profile associated with lupus nephritis (LN). The three ncRNA types with the highest number of differentially expressed transcripts were microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and piwi-interacting RNAs (piRNAs). We identified an exosomal 29-ncRNA molecular signature, of which 15 were associated only with LN presence, piRNAs were the most representative, followed by lncRNAs and miRNAs. The transcriptional regulatory network showed a significant role for four lncRNAs (LINC01015, LINC01986, AC087257.1 and AC022596.1) and two miRNAs (miR-16-5p and miR-101-3p) in network organization, targeting critical pathways implicated in inflammation, fibrosis, epithelial-mesenchymal transition and actin cytoskeleton. From these, a handful of potential targets, such as transforming growth factor-beta (TGF-beta) superfamily binding proteins (activin-A, TGFB receptors, etc.), WNT/beta-catenin and fibroblast growth factors (FGFs) have been identified for use as therapeutic targets of renal damage in SLE.

2023

artículo original

10.3390/ijms24087088

PDF

systemic lupus erythematosus

exosomes

non-coding RNA

RNA sequencing

bioinformatics enrichment analysis

Bioquímica y biología molecular

Química

lupus eritematoso sistémico

exosomas

ARN no codificante

secuenciación de ARN

análisis de enriquecimiento bioinformático

artículo original

versión publicada

CC BY 4.0

CC BY 4.0

acceso abierto

acceso abierto

WOS:000979318900001

verde# dorado

Bioquímica y biología molecular

Química

ISCIII PI18/01405

ISCIII PI21/00249

FI20/00096

FI22/00032

MICINN PID2020-117114GB-I00

ANID NCS2021_013