Dynamic changes in extracellular vesicle-associated miRNAs elicited by ultrasound in inflammatory bowel disease patients.

Autor: Tran F; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany. f.tran@ikmb.uni-kiel.de.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105, Kiel, Germany. f.tran@ikmb.uni-kiel.de., Scharmacher A; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany., Baran N; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany., Mishra N; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany., Wozny M; Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Italy., Chavez SP; Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Italy., Bhardwaj A; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany., Hinz S; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105, Kiel, Germany., Juzenas S; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany.; Institute of Biotechnology, Life Science Centre, Vilnius University, Vilnius, Lithuania., Bernardes JP; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany., Sievers LK; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105, Kiel, Germany., Lessing M; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105, Kiel, Germany., Aden K; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105, Kiel, Germany., Lassen A; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105, Kiel, Germany., Bergfeld A; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105, Kiel, Germany., Weber HJ; Department of Gastroenterology, Asklepios Westklinikum, 22559, Hamburg, Germany.; Institute of Infection Medicine, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, 24105, Kiel, Germany., Neas L; Department of Internal Medicine III, University Medical Center Schleswig-Holstein, 24105, Kiel, Germany., Vetrano S; Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, Italy.; IBD Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089, Rozzano, Italy., Schreiber S; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, 24105, Kiel, Germany., Rosenstiel P; Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Christian Albrecht University Kiel, Campus Kiel, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 May 13; Vol. 14 (1), pp. 10925. Date of Electronic Publication: 2024 May 13.
DOI: 10.1038/s41598-024-61532-2
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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