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NETs also contribute to the pathogenesis and exacerbation of sepsis. Although the lung is highly vulnerable to infections, few studies have explored the role of NETs in sepsis\u2010induced acute lung injury (SI\u2010ALI). We demonstrate that NETs induce SI\u2010ALI via enhanced ferroptosis in alveolar epithelial cells. Our findings reveal that the excessive release of NETs in patients and mice with SI\u2010ALI is accompanied by upregulation of ferroptosis depending on METTL3\u2010induced m6A modification of hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) and subsequent mitochondrial metabolic reprogramming. In addition to conducting METTL3 overexpression and knockdown experiments in vitro, we also investigated the impact of ferroptosis on SI\u2010ALI caused by NETs in a caecum ligation and puncture (CLP)\u2010induced SI\u2010ALI model using METTL3 condition knockout (CKO) mice and wild\u2010type mice.\u00a0Our results indicate the crucial role of NETs in the progression of SI\u2010ALI via NET\u2010activated METTL3 m6A\u2010IGF2BP2\u2010dependent m6A modification of HIF\u20101\u03b1, which further contributes to metabolic reprogramming and ferroptosis in alveolar epithelial cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.1389","type":"journal-article","created":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T01:49:33Z","timestamp":1694828973000},"source":"Crossref","is-referenced-by-count":134,"title":["METTL3\u2010mediated N6\u2010methyladenosine exacerbates ferroptosis via m6A\u2010IGF2BP2\u2010dependent mitochondrial metabolic reprogramming in sepsis\u2010induced acute lung injury"],"prefix":"10.1002","volume":"13","author":[{"given":"Hao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Perioperative Stress and Protection  Shanghai China"},{"name":"Department of Anesthesiology Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Perioperative Stress and Protection  Shanghai China"},{"name":"Department of Anesthesiology Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanghanzhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology 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