hUC-MSC-EV-miR-24 enhances the protective effect of dexmedetomidine preconditioning against myocardial ischemia-reperfusion injury through the KEAP1/Nrf2/HO-1 signaling.

Dexmedetomidine Extracellular vesicles Human umbilical cord mesenchymal stem cells Ischemic-reperfusion injury KEAP1 Macrophage polarization Nrf2/HO-1 signaling pathway microRNA-24

Journal

Drug delivery and translational research
ISSN: 2190-3948
Titre abrégé: Drug Deliv Transl Res
Pays: United States
ID NLM: 101540061

Informations de publication

Date de publication:
04 Aug 2023
Historique:
accepted: 07 07 2023
medline: 4 8 2023
pubmed: 4 8 2023
entrez: 4 8 2023
Statut: aheadofprint

Résumé

The cardioprotective effect of microRNAs (miRNAs) on myocardial ischemic-reperfusion (I/R) injury has been documented. Here, we aim to decipher the mechanism of miR-24 delivered by human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSC-EVs) in myocardial I/R injury after dexmedetomidine (DEX) preconditioning. We collected and identified hUC-MSCs and extracted EVs, which were co-cultured with DEX-preconditioned hypoxia/reoxygenation (H/R) cardiomyocyte models or injected into I/R mouse models. The cardiomyocytes and myocardial injury were evaluated by molecular biology experiments. miR-24 was highly expressed in hUC-MSC-EVs. hUC-MSC-EVs could transfer miR-24 into cardiomyocytes where miR-24 augmented cell viability and inhibited cell apoptosis after DEX preconditioning. In the co-culture system of RAW264.7 macrophages with hUC-MSC-EVs, miR-24 promoted M2-type polarization of macrophages and reduced M1-type macrophage polarization. Mechanistically, miR-24 targeted KEAP1 and inhibited its expression, resulting in disruption of the Nrf2/HO-1 signaling. In vivo data confirmed that miR-24 delivered by hUC-MSC-EVs enhanced the suppressing effect of DEX preconditioning on inflammation and apoptosis in rats following myocardial I/R injury. Overall, miR-24 delivered by hUC-MSC-EVs can promote M2 polarization of macrophages and enhance the protective effect of DEX preconditioning on myocardial I/R injury by down-regulating the KEAP1/Nrf2/HO-1 signaling axis.

Identifiants

DOI: 10.1007/s13346-023-01388-7 PMID: 37540334
pubmed: 37540334
doi: 10.1007/s13346-023-01388-7
pii: 10.1007/s13346-023-01388-7
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Excellent Youth Foundation of Hunan Provincial Department of Education
ID : 19B477
Organisme : Project of Hunan Provincial Health Commission
ID : 20200018
Organisme : Project of Hunan Provincial Health Commission
ID : 20200037
Organisme : Natural Science Foundation of Hunan Province
ID : 2021JJ70043
Organisme : Guiding project of Hengyang science and Technology Bureau
ID : 202121034637

Informations de copyright

© 2023. Controlled Release Society.

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Auteurs

Zixin Hou (Z)

Department of Anesthesiology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, 421001, People's Republic of China.

Fengrui Yang (F)

Department of Anesthesiology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, 421001, People's Republic of China.
Department of Anesthesiology, Hengyang Medical School, Affiliated Huaihua Hospital, University of South China, Huaihua, 418000, People's Republic of China.

Kemin Chen (K)

Department of Anesthesiology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, 421001, People's Republic of China.

Yuxia Wang (Y)

Department of Anesthesiology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, 421001, People's Republic of China.

Jie Qin (J)

Department of Anesthesiology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, 421001, People's Republic of China.

Feng Liang (F)

Department of Anesthesiology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, 421001, People's Republic of China. 275449729@qq.com.

Classifications MeSH