EVs-miR-17-5p attenuates the osteogenic differentiation of vascular smooth muscle cells potentially via inhibition of TGF-β signaling under high glucose conditions.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
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

16323

Subventions

Organisme : JSPS KAKENHI
ID : JP21H02916
Organisme : CREST
ID : JPMJCR17H5

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Isashi Baba (I)

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Tetsuya Matoba (T)

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. matoba@cardiol.med.kyushu-u.ac.jp.

Shunsuke Katsuki (S)

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Jun-Ichiro Koga (JI)

Second Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

Takuro Kawahara (T)

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Mitsukuni Kimura (M)

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Hidetaka Akita (H)

Laboratory of Drug Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.

Hiroyuki Tsutsui (H)

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

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