{
  "abstract": "The molecular mechanism by which hypoxia-inducible factor 1-alpha (HIF-1α) regulates asthma pathogenesis through modulation of neutrophil extracellular trap (NET) formation remains poorly defined. Given that NETs act as core drivers of allergic asthma pathology by amplifying airway inflammation and inducing airway epithelial ferroptosis, this study aimed to elucidate the regulatory axis involving airway epithelial cell-derived exosomal miR-146a-3p. We proposed that exosomal miR-146a-3p directly targets HIF-1α to suppress the transcriptional activity of its downstream target gene ELANE , thereby blocking NETs formation and ultimately alleviating asthmatic airway inflammation. Using public transcriptomic data from asthma patients, we identified miR-146a-3p as significantly downregulated in asthmatic tissues. BEAS-2B cell-derived exosomes were isolated via differential centrifugation. Employing a PMA-induced neutrophil inflammation model and an HDM/NETs-challenged asthmatic mouse model, we systematically demonstrated that BEAS-2B cell-derived exosomes function as efficient delivery vehicles for miR-146a-3p, transporting it into neutrophils. By targeting and inhibiting HIF-1α nucleocytoplasmic translocation and its transcriptional activation capacity, exosomal miR-146a-3p significantly downregulated the expression of NE—key mediator of NET formation—thereby blocking aberrant NETs release. Moreover, we confirmed that NETs reduction modulates the cGAS-STING signaling pathway, reverses the aberrant expression patterns of the ferroptosis regulatory proteins GPX4, SLC7A11, and ACSL4, maintains cellular iron homeostasis, and subsequently alleviates airway epithelial ferroptosis, ultimately ameliorating asthmatic airway inflammation. Collectively, this study reveals a novel mechanism by which excessive NET accumulation exacerbates asthma pathology through cGAS-STING-mediated airway epithelial ferroptosis. Furthermore, it identifies BEAS-2B cell-derived exosomal miR-146a-3p as a key regulatory molecule and potential therapeutic target, offering a new theoretical framework and intervention strategy for understanding and treating allergic asthma.",
  "abstract_shown": true,
  "affiliations": [
    "Jilin Key Laboratory for Immune and Targeting Research on Common Allergic, Diseases, Yanbian University, Yanji, 133002, PR China; Department of Anatomy, Histology and Embryology, Yanbian University Medical, College, Yanji, 133002, PR China",
    "Jilin Key Laboratory for Immune and Targeting Research on Common Allergic, Diseases, Yanbian University, Yanji, 133002, PR China; Department of Traditional Chinese Medicine, Yanbian University Medicine College, Yanji, 133002, PR China",
    "Yanbian University Agriculture College, Yanji, 133002, PR China",
    "Jilin Key Laboratory for Immune and Targeting Research on Common Allergic, Diseases, Yanbian University, Yanji, 133002, PR China; Department of Traditional Chinese Medicine, Yanbian University Medicine College, Yanji, 133002, PR China; Corresponding author. Department of Traditional Chinese Medicine, Yanbian University Medical College, No. 977, Gongyuan Road, Yanji, 133002, PR China."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jianing Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yunong Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhien Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Mingyue Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yedong Xiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Feifei Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yulian Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Guanhao Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Jingmei Chai"
    },
    {
      "name": "Guanghai Yan"
    },
    {
      "name": "Chongyang Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bq9q22j8j70y8.bib",
  "cited_by": 0,
  "doi": "10.1016/j.redox.2026.104455",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2213231726004544",
  "id": "bq9q22j8j70y8",
  "issns": [
    "2213-2317"
  ],
  "landing_url": "https://doi.org/10.1016/j.redox.2026.104455",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "lcc",
      "R5-920"
    ],
    [
      "openalex",
      "2737|Asthma and respiratory diseases"
    ]
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  "openalex": "W7223668293",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2213231726004544/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-02",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/bq9q22j8j70y8.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T14:21:09Z",
      "native_id": "0172981d62514fa4a72cf7c28a8d1100",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.redox.2026.104455"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Asthma and respiratory diseases",
      "subfield": "physiology"
    }
  ],
  "title": "Exosomal miR-146a-3p from BEAS-2B cells alleviates NETs-Aggravated asthma by targeting HIF-1α to inhibit ferroptosis",
  "title_text": "Exosomal miR-146a-3p from BEAS-2B cells alleviates NETs-Aggravated asthma by targeting HIF-1α to inhibit ferroptosis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T14:20:11Z",
  "url": "https://research.draconitic.com/paper/bq9q22j8j70y8",
  "venue": "Redox Biology",
  "versions": []
}