{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:13:23Z","timestamp":1790712803738,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["RO1 HL140470\u20100181"],"award-info":[{"award-number":["RO1 HL140470\u20100181"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Post\u2010lung transplant (LTx) injury can involve sterile inflammation due to ischemia\u2013reperfusion injury (IRI) that contributes to allograft dysfunction. In this study, we investigated the cell\u2010specific role of ferroptosis (excessive iron\u2010mediated cell death) in mediating lung IRI and investigated if specialized pro\u2010resolving mediators such as Lipoxin A4 (LxA\n                    <jats:sub>4<\/jats:sub>\n                    ) can protect against ferroptosis in lung IRI. Single\u2010cell RNA sequencing analysis of lung tissue from post\u2010LTx patients was performed, and lung IRI was evaluated in C57BL\/6 (WT), formyl peptide receptor 2 knockout (\n                    <jats:italic>Fpr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) and nuclear factor erythroid 2\u2010related factor 2 knockout (\n                    <jats:italic>Nrf2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) mice using a hilar\u2010ligation model with or without LxA\n                    <jats:sub>4<\/jats:sub>\n                    administration. Furthermore, the protective efficacy of LxA\n                    <jats:sub>4<\/jats:sub>\n                    was evaluated employing a murine orthotopic LTx model and in\u00a0vitro studies using alveolar type II epithelial (ATII) cells. The results show differential expression of ferroptosis\u2010related genes in post\u2010LTx patient samples compared to healthy controls. A significant increase in the levels of oxidized lipids and a reduction in the levels of intact lipids were observed in mice subjected to IRI compared to shams. Importantly, LxA\n                    <jats:sub>4<\/jats:sub>\n                    treatment attenuated pulmonary dysfunction, ferroptosis, and inflammation in WT mice subjected to lung IRI, but not in\n                    <jats:italic>Fpr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    or\n                    <jats:italic>Nrf2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice after IRI. In the murine LTx model, LxA\n                    <jats:sub>4<\/jats:sub>\n                    treatment increased PaO\n                    <jats:sub>2<\/jats:sub>\n                    levels and attenuated lung IRI. Mechanistically, LxA\n                    <jats:sub>4<\/jats:sub>\n                    \u2010mediated protection involves an increase in NRF2 activation and glutathione concentration as well as a decrease in MDA levels in ATII cells. In summary, our results collectively show that LxA\n                    <jats:sub>4<\/jats:sub>\n                    \/FPR2 signaling on ATII cells mitigates ferroptosis via NRF2 activation and protects against lung IRI.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401475r","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:15:39Z","timestamp":1745471739000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Lipoxin\n                    <scp>\n                      A\n                      <sub>4<\/sub>\n                    <\/scp>\n                    \/\n                    <scp>FPR2<\/scp>\n                    Signaling Mitigates Ferroptosis of Alveolar Epithelial Cells via\n                    <scp>NRF2<\/scp>\n                    \u2010Dependent Pathway During Lung Ischemia\u2013Reperfusion Injury"],"prefix":"10.1096","volume":"39","author":[{"given":"Denny Joseph Manual","family":"Kollareth","sequence":"first","affiliation":[{"name":"Department of Surgery University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1025-1888","authenticated-orcid":false,"given":"Victoria","family":"Leroy","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxiao","family":"Tu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makena Jade","family":"Woolet\u2010Stockton","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manasi","family":"Kamat","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Garrett","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoshuai","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Florida  Gainesville 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