EVs-miR-17-5p attenuates the osteogenic differentiation of vascular smooth muscle cells potentially via inhibition of TGF-β signaling under high glucose conditions.
MicroRNAs
/ genetics
Animals
Muscle, Smooth, Vascular
/ metabolism
Glucose
/ pharmacology
Osteogenesis
/ drug effects
Transforming Growth Factor beta
/ metabolism
Mice
Cell Differentiation
Signal Transduction
Myocytes, Smooth Muscle
/ metabolism
Extracellular Vesicles
/ metabolism
Vascular Calcification
/ metabolism
Receptor, Transforming Growth Factor-beta Type II
/ metabolism
Male
Mice, Inbred C57BL
Core Binding Factor Alpha 1 Subunit
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
15 Jul 2024
15 Jul 2024
Historique:
received:
12
07
2023
accepted:
08
07
2024
medline:
16
7
2024
pubmed:
16
7
2024
entrez:
15
7
2024
Statut:
epublish
Résumé
Vascular calcification, which is a major complication of diabetes mellitus, is an independent risk factor for cardiovascular disease. Osteogenic differentiation of vascular smooth muscle cells (VSMCs) is one of the key mechanisms underlying vascular calcification. Emerging evidence suggests that macrophage-derived extracellular vesicles (EVs) may be involved in calcification within atherosclerotic plaques in patients with diabetes mellitus. However, the role of macrophage-derived EVs in the progression of vascular calcification is largely unknown. In this study, we investigated whether macrophage-derived EVs contribute to the osteogenic differentiation of VSMCs under high glucose conditions. We isolated EVs that were secreted by murine peritoneal macrophages under normal glucose (EVs-NG) or high glucose (EVs-HG) conditions. miRNA array analysis in EVs from murine macrophages showed that miR-17-5p was significantly increased in EVs-HG compared with EVs-NG. Prediction analysis with miRbase identified transforming growth factor β receptor type II (TGF-β RII) as a potential target of miR-17-5p. EVs-HG as well as miR-17-5p overexpression with lipid nanoparticles inhibited the gene expression of Runx2, and TGF-β RII. Furthermore, we demonstrated that VSMCs transfected with miR-17-5p mimic inhibited calcium deposition. Our findings reveal a novel role of macrophage-derived EVs in the negative regulation of osteogenic differentiation in VSMCs under high glucose conditions.
Identifiants
pubmed: 39009669
doi: 10.1038/s41598-024-67006-9
pii: 10.1038/s41598-024-67006-9
doi:
Substances chimiques
MicroRNAs
0
Glucose
IY9XDZ35W2
Transforming Growth Factor beta
0
Mirn17 microRNA, mouse
0
Receptor, Transforming Growth Factor-beta Type II
EC 2.7.11.30
Tgfbr2 protein, mouse
EC 2.7.11.30
Core Binding Factor Alpha 1 Subunit
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
16323Subventions
Organisme : JSPS KAKENHI
ID : JP21H02916
Organisme : CREST
ID : JPMJCR17H5
Informations de copyright
© 2024. The Author(s).
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