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BMSC‑derived exosome‑mediated miR‑25‑3p delivery protects against myocardial ischemia/reperfusion injury by constraining M1‑like macrophage polarization

  • Authors:
    • Jingxia Du
    • Yibo Dong
    • Jingjing Song
    • Hanqi Shui
    • Chengyao Xiao
    • Yue Hu
    • Shiyao Zhou
    • Shanshan Wang
  • View Affiliations / Copyright

    Affiliations: College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China
    Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 142
    |
    Published online on: June 18, 2024
       https://doi.org/10.3892/mmr.2024.13266
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Abstract

Myocardial ischemia/reperfusion injury (MIRI) is a significant challenge in the management of myocardial ischemic disease. Extensive evidence suggests that the macrophage‑mediated inflammatory response may play a vital role in MIRI. Mesenchymal stem cells and, in particular, exosomes derived from these cells, may be key mediators of myocardial injury and repair. However, whether exosomes protect the heart by regulating the polarization of macrophages and the exact mechanisms involved are poorly understood. The present study aimed to determine whether exosomes secreted by bone marrow mesenchymal stem cells (BMSC‑Exo) harboring miR‑25‑3p can alter the phenotype of macrophages by affecting the JAK2/STAT3 signaling pathway, which reduces the inflammatory response and protects against MIRI. An in vivo MIRI model was established in rats by ligating the anterior descending region of the left coronary artery for 30 min followed by reperfusion for 120 min, and BMSC‑Exo carrying miR‑25‑3p (BMSC‑Exo‑25‑3p) were administered through tail vein injection. A hypoxia‑reoxygenation model of H9C2 cells was established, and the cells were cocultured with BMSC‑Exo‑25‑3p in vitro. The results of the present study demonstrated that BMSC‑Exo or BMSC‑Exo‑25‑3p could be taken up by cardiomyocytes in vivo and H9C2 cells in vitro. BMSC‑Exo‑25‑3p demonstrated powerful cardioprotective effects by decreasing the cardiac infarct size, reducing the incidence of malignant arrhythmias and attenuating myocardial enzyme activity, as indicated by lactate dehydrogenase and creatine kinase levels. It induced M1‑like macrophage polarization after myocardial ischemia/reperfusion (I/R), as evidenced by the increase in iNOS expression through immunofluorescence staining and upregulation of proinflammatory cytokines through RT‑qPCR, such as interleukin‑1β (IL‑1β) and interleukin‑6 (IL‑6). As hypothesized, BMSC‑Exo‑25‑3p inhibited M1‑like macrophage polarization and proinflammatory cytokine expression while promoting M2‑like macrophage polarization. Mechanistically, the JAK2/STAT3 signaling pathway was activated after I/R in vivo and in LPS‑stimulated macrophages in vitro, and BMSC‑Exo‑25‑3p pretreatment inhibited this activation. The results of the present study indicate that the attenuation of MIRI by BMSC‑Exo‑25‑3p may be related to JAK2/STAT3 signaling pathway inactivation and subsequent inhibition of M1‑like macrophage polarization.
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Copy and paste a formatted citation
Spandidos Publications style
Du J, Dong Y, Song J, Shui H, Xiao C, Hu Y, Zhou S and Wang S: BMSC‑derived exosome‑mediated miR‑25‑3p delivery protects against myocardial ischemia/reperfusion injury by constraining M1‑like macrophage polarization. Mol Med Rep 30: 142, 2024.
APA
Du, J., Dong, Y., Song, J., Shui, H., Xiao, C., Hu, Y. ... Wang, S. (2024). BMSC‑derived exosome‑mediated miR‑25‑3p delivery protects against myocardial ischemia/reperfusion injury by constraining M1‑like macrophage polarization. Molecular Medicine Reports, 30, 142. https://doi.org/10.3892/mmr.2024.13266
MLA
Du, J., Dong, Y., Song, J., Shui, H., Xiao, C., Hu, Y., Zhou, S., Wang, S."BMSC‑derived exosome‑mediated miR‑25‑3p delivery protects against myocardial ischemia/reperfusion injury by constraining M1‑like macrophage polarization". Molecular Medicine Reports 30.2 (2024): 142.
Chicago
Du, J., Dong, Y., Song, J., Shui, H., Xiao, C., Hu, Y., Zhou, S., Wang, S."BMSC‑derived exosome‑mediated miR‑25‑3p delivery protects against myocardial ischemia/reperfusion injury by constraining M1‑like macrophage polarization". Molecular Medicine Reports 30, no. 2 (2024): 142. https://doi.org/10.3892/mmr.2024.13266
Copy and paste a formatted citation
x
Spandidos Publications style
Du J, Dong Y, Song J, Shui H, Xiao C, Hu Y, Zhou S and Wang S: BMSC‑derived exosome‑mediated miR‑25‑3p delivery protects against myocardial ischemia/reperfusion injury by constraining M1‑like macrophage polarization. Mol Med Rep 30: 142, 2024.
APA
Du, J., Dong, Y., Song, J., Shui, H., Xiao, C., Hu, Y. ... Wang, S. (2024). BMSC‑derived exosome‑mediated miR‑25‑3p delivery protects against myocardial ischemia/reperfusion injury by constraining M1‑like macrophage polarization. Molecular Medicine Reports, 30, 142. https://doi.org/10.3892/mmr.2024.13266
MLA
Du, J., Dong, Y., Song, J., Shui, H., Xiao, C., Hu, Y., Zhou, S., Wang, S."BMSC‑derived exosome‑mediated miR‑25‑3p delivery protects against myocardial ischemia/reperfusion injury by constraining M1‑like macrophage polarization". Molecular Medicine Reports 30.2 (2024): 142.
Chicago
Du, J., Dong, Y., Song, J., Shui, H., Xiao, C., Hu, Y., Zhou, S., Wang, S."BMSC‑derived exosome‑mediated miR‑25‑3p delivery protects against myocardial ischemia/reperfusion injury by constraining M1‑like macrophage polarization". Molecular Medicine Reports 30, no. 2 (2024): 142. https://doi.org/10.3892/mmr.2024.13266
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