Targeting DECR1 Mitigates Ferroptosis in Airway Epithelial Cells and Promotes Inflammation Resolution in Asthma

Le résumé fourni par la source

Asthma is characterized by persistent airway inflammation, and ferroptosis is closely related to this pathological manifestation. Although studies have explored the inducing factors of asthmatic inflammation, the regulatory mechanisms during the resolution phase and the role of ferroptosis in it remain unclear. In this study, proteomics was performed to characterize functional alterations in intrapulmonary airway epithelial cells during the resolution phase in an ovalbumin (OVA)-induced inflammation mouse model. The correlations among DECR1, ferroptosis, and airway inflammation were analyzed. The effects of DECR1 knockdown on ferroptosis and epithelial function, and the regulatory mechanism were examined in vitro. The impact of recombinant DECR1 administration and adeno-associated virus (AAV)-mediated DECR1 overexpression on inflammation resolution was evaluated in vivo. Finally, DECR1 levels in asthma patients were measured and correlated with clinical parameters. We demonstrated that the proteome underwent significant changes during the inflammation resolution phase in mice with OVA-induced airway inflammation, with DECR1 showing a marked decrease at the peak of inflammation and recovered during resolution. DECR1 levels were negatively correlated with airway inflammation and ferroptosis-associated markers. In vitro, our results confirmed that DECR1 deficiency induced ferroptosis and disrupted epithelial function by upregulating DUOXA1. In vivo, recombinant DECR1 administration or AAV-mediated DECR1 overexpression alleviated airway inflammation and accelerated resolution through mediating epithelial ferroptosis. Consistently, DECR1 levels were also reduced in asthma patients and positively correlated with lung function. Together, DECR1 regulates epithelial ferroptosis through DUOXA1-dependent mechanisms, thereby preserving epithelial integrity and promoting inflammation resolution. Targeting DECR1 may offer a novel therapeutic strategy for asthma.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.