Dynamic changes in extracellular vesicle-associated miRNAs elicited by ultrasound in inflammatory bowel disease patients.
Biomarker discovery
Extracellular vesicles
Inflammatory bowel disease
Liquid biopsies
Sonography
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 05 2024
13 05 2024
Historique:
received:
29
02
2024
accepted:
07
05
2024
medline:
14
5
2024
pubmed:
14
5
2024
entrez:
13
5
2024
Statut:
epublish
Résumé
Blood-based biomarkers that reliably indicate disease activity in the intestinal tract are an important unmet need in the management of patients with IBD. Extracellular vesicles (EVs) are cell-derived membranous microparticles, which reflect the cellular and functional state of their site of site of origin. As ultrasound waves may lead to molecular shifts of EV contents, we hypothesized that application of ultrasound waves on inflamed intestinal tissue in IBD may amplify the inflammation-specific molecular shifts in EVs like altered EV-miRNA expression, which in turn can be detected in the peripheral blood. 26 patients with IBD were included in the prospective clinical study. Serum samples were collected before and 30 min after diagnostic transabdominal ultrasound. Differential miRNA expression was analyzed by sequencing. Candidate inducible EV-miRNAs were functionally assessed in vitro by transfection of miRNA mimics and qPCR of predicted target genes. Serum EV-miRNA concentration at baseline correlated with disease severity, as determined by clinical activity scores and sonographic findings. Three miRNAs (miR-942-5p, mir-5588, mir-3195) were significantly induced by sonography. Among the significantly regulated EV-miRNAs, miR-942-5p was strongly induced in higher grade intestinal inflammation and correlated with clinical activity in Crohn's disease. Prediction of target regulation and transfection of miRNA mimics inferred a role of this EV-miRNA in regulating barrier function in inflammation. Induction of mir-5588 and mir-3195 did not correlate with inflammation grade. This proof-of-concept trial highlights the principle of induced molecular shifts in EVs from inflamed tissue through transabdominal ultrasound. These inducible EVs and their molecular cargo like miRNA could become novel biomarkers for intestinal inflammation in IBD.
Identifiants
pubmed: 38740826
doi: 10.1038/s41598-024-61532-2
pii: 10.1038/s41598-024-61532-2
doi:
Substances chimiques
MicroRNAs
0
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
10925Subventions
Organisme : Innovative Medicines Initiative
ID : 853995
Organisme : Bundesministerium für Bildung und Forschung
ID : 01ZX1902A
Organisme : Deutsche Forschungsgemeinschaft
ID : 390884018
Informations de copyright
© 2024. The Author(s).
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