hUC-MSC-EV-miR-24 enhances the protective effect of dexmedetomidine preconditioning against myocardial ischemia-reperfusion injury through the KEAP1/Nrf2/HO-1 signaling
© 2023. Controlled Release Society..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Drug delivery and translational research - 14(2023), 1 vom: 21. Jan., Seite 143-157 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hou, Zixin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.12.2023 Date Revised 25.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s13346-023-01388-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360400299 |
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| 245 | 1 | 0 | |a hUC-MSC-EV-miR-24 enhances the protective effect of dexmedetomidine preconditioning against myocardial ischemia-reperfusion injury through the KEAP1/Nrf2/HO-1 signaling |
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| 520 | |a © 2023. Controlled Release Society. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Dexmedetomidine | |
| 650 | 4 | |a Extracellular vesicles | |
| 650 | 4 | |a Human umbilical cord mesenchymal stem cells | |
| 650 | 4 | |a Ischemic-reperfusion injury | |
| 650 | 4 | |a KEAP1 | |
| 650 | 4 | |a Macrophage polarization | |
| 650 | 4 | |a Nrf2/HO-1 signaling pathway | |
| 650 | 4 | |a microRNA-24 | |
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| 650 | 7 | |a MIRN24 microRNA, human |2 NLM | |
| 650 | 7 | |a KEAP1 protein, rat |2 NLM | |
| 650 | 7 | |a MIRN24 microRNA, rat |2 NLM | |
| 700 | 1 | |a Yang, Fengrui |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Kemin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuxia |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Feng |e verfasserin |4 aut | |
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