Exosomal miR-146a-3p from BEAS-2B cells alleviates NETs-Aggravated asthma by targeting HIF-1α to inhibit ferroptosis

@article{yang2026exosomal,
  title = {{Exosomal miR-146a-3p from BEAS-2B cells alleviates NETs-Aggravated asthma by targeting HIF-1α to inhibit ferroptosis}},
  author = {Jianing Yang and Yunong Li and Zhien Li and Mingyue Liu and Yedong Xiang and Feifei Xu and Yulian Zhang and Guanhao Li and Jingmei Chai and Guanghai Yan and Chongyang Wang},
  journal = {Redox Biology},
  year = {2026},
  month = nov,
  doi = {10.1016/j.redox.2026.104455},
  url = {https://doi.org/10.1016/j.redox.2026.104455},
  note = {CC BY},
}

TY  - JOUR
TI  - Exosomal miR-146a-3p from BEAS-2B cells alleviates NETs-Aggravated asthma by targeting HIF-1α to inhibit ferroptosis
AU  - Jianing Yang
AU  - Yunong Li
AU  - Zhien Li
AU  - Mingyue Liu
AU  - Yedong Xiang
AU  - Feifei Xu
AU  - Yulian Zhang
AU  - Guanhao Li
AU  - Jingmei Chai
AU  - Guanghai Yan
AU  - Chongyang Wang
PY  - 2026
DA  - 2026/11/02
JO  - Redox Biology
DO  - 10.1016/j.redox.2026.104455
UR  - https://doi.org/10.1016/j.redox.2026.104455
AB  - 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.
SN  - 2213-2317
ER  -