The miR-125a-5p/IRF4 Axis Mediates Sodium Arsenite-Induced M2 Macrophage Polarization
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Le résumé fourni par la source
Arsenic, a ubiquitous metalloid, is commonly found in surface waters; as well as serious human health issues, it also induces systemic diseases and carcinogenesis upon chronic exposure. To better understand how arsenic potentially alters the immune system, it is important to study its effects on macrophage polarization. Micro-RNA plays an epigenetic regulatory role in organisms. The miR-125 family regulates macrophage polarization and tumorigenesis, yet its role in arsenic-induced macrophage polarization remains unexplored. This study investigated the mechanism of sodium arsenite (NaAsO2)-driven macrophage polarization via miR-125a-5p. In vivo, rats exposed to 10 or 50 mg/L NaAsO2 for 12 weeks exhibited elevated M2 markers (CD206, Arg1) and reduced M1 markers (iNOS, IL-1β, TNF-α) in liver and bladder tissues. In vitro, THP-1-derived macrophages treated with NaAsO2 (2–8 μM) for 48 h showed dose-dependent M2 polarization, marked by upregulated CD206, Arg1, and IL-10. Flow cytometry results show that the proportion of M2/M1-type cells has increased significantly. Notably, NaAsO2 suppressed miR-125a-5p expression and elevated interferon regulatory factor 4 (IRF4), a predicted target of miR-125a-5p. Overexpression of miR-125a-5p reversed NaAsO2-induced M2 polarization by inhibiting IRF4, thereby reducing M2 markers and restoring M1-associated proteins. These findings reveal that NaAsO2 promotes M2 macrophage polarization through the miR-125a-5p/IRF4 axis, highlighting a novel epigenetic mechanism in arsenic-associated tumor microenvironments and immune dysfunction. This study provides critical insights into targeting miR-125a-5p as a therapeutic strategy.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- The miR-125a-5p/IRF4 Axis Mediates Sodium Arsenite-Induced M2 Macrophage Polarization
- Date Crossref
- 20/11/2025
- Éditeur
- MDPI AG
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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China Medical University Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention pays non établi dans la noticeUniversité ou école supérieure
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Ministry of Ecology and Environment pays non établi dans la noticeOrganisme public
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School of Public Health Department of Environmental Health pays non établi dans la noticeUniversité ou école supérieure
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Key Laboratory of Environmental Pollution Health Risk Assessment pays non établi dans la noticeStructure de recherche
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Liaoning Key Laboratory of Environmental Health Damage Research and Assessment pays non établi dans la noticeStructure de recherche
Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention — China Medical University, Ministry of Ecology and Environment et Department of Environmental Health — School of Public Health, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.