{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T23:18:33Z","timestamp":1778627913338,"version":"3.51.4"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":49,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, and Future Planning","award":["NRF-2014R1A1A1038278"],"award-info":[{"award-number":["NRF-2014R1A1A1038278"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-45319-1","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T02:47:25Z","timestamp":1774406845000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["EphA2 monoclonal antibody attenuates hyperoxia-induced acute lung injury by preserving the alveolar\u2013endothelial barrier"],"prefix":"10.1038","volume":"16","author":[{"given":"Kyung Soo","family":"Chung","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju Hye","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su Hwan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ah Young","family":"Leem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moo Suk","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Seok","family":"Moon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Sam","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"45319_CR1","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1186\/s13054-021-03815-y","volume":"25","author":"M Singer","year":"2021","unstructured":"Singer, M. et al. Dangers of hyperoxia. Crit. Care 25, 440. https:\/\/doi.org\/10.1186\/s13054-021-03815-y (2021).","journal-title":"Crit. Care"},{"key":"45319_CR2","doi-asserted-by":"publisher","first-page":"104393","DOI":"10.1016\/j.amsu.2022.104393","volume":"81","author":"EE Lius","year":"2022","unstructured":"Lius, E. E. & Syafaah, I. Hyperoxia in the management of respiratory failure: A literature review. Ann. Med. Surg. (Lond.) 81, 104393. https:\/\/doi.org\/10.1016\/j.amsu.2022.104393 (2022).","journal-title":"Ann. Med. Surg. (Lond.)"},{"key":"45319_CR3","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.pccm.2024.04.002","volume":"2","author":"Y Su","year":"2024","unstructured":"Su, Y., Lucas, R., Fulton, D. J. R. & Verin, A. D. Mechanisms of pulmonary endothelial barrier dysfunction in acute lung injury and acute respiratory distress syndrome. Chin. Med. J. Pulmonary Crit. Care Med. 2, 80\u201387. https:\/\/doi.org\/10.1016\/j.pccm.2024.04.002 (2024).","journal-title":"Chin. Med. J. Pulmonary Crit. Care Med."},{"key":"45319_CR4","doi-asserted-by":"publisher","first-page":"1603287","DOI":"10.3389\/fphar.2025.1603287","volume":"16","author":"F Wang","year":"2025","unstructured":"Wang, F. et al. Oxidative stress in ARDS: Mechanisms and therapeutic potential. Front. Pharmacol. 16, 1603287. https:\/\/doi.org\/10.3389\/fphar.2025.1603287 (2025).","journal-title":"Front. Pharmacol."},{"key":"45319_CR5","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1056\/NEJMoa2032510","volume":"384","author":"OL Schj\u00f8rring","year":"2021","unstructured":"Schj\u00f8rring, O. L. et al. Lower or higher oxygenation targets for acute hypoxemic respiratory failure. N. Engl. J. Med. 384, 1301\u20131311. https:\/\/doi.org\/10.1056\/NEJMoa2032510 (2021).","journal-title":"N. Engl. J. Med."},{"key":"45319_CR6","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13613-024-01300-7","volume":"14","author":"X Li","year":"2024","unstructured":"Li, X. et al. Conservative versus liberal oxygen therapy for intensive care unit patients: Meta-analysis of randomized controlled trials. Ann. Intensive Care 14, 68. https:\/\/doi.org\/10.1186\/s13613-024-01300-7 (2024).","journal-title":"Ann. Intensive Care"},{"key":"45319_CR7","doi-asserted-by":"publisher","first-page":"e25","DOI":"10.1097\/JTCCM-D-25-00005","volume":"7","author":"J Wang","year":"2025","unstructured":"Wang, J. et al. Conservative versus liberal oxygen therapy for critically ill patients: A meta-analysis with trial sequential analysis and clinical recommendations. J. Transl. Crit. Care Med. 7, e25. https:\/\/doi.org\/10.1097\/JTCCM-D-25-00005 (2025).","journal-title":"J. Transl. Crit. Care Med."},{"key":"45319_CR8","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1007\/s00134-024-07554-w","volume":"50","author":"PJ Young","year":"2024","unstructured":"Young, P. J. Less is best for oxygen therapy in adults in the intensive care unit with severe hypoxaemia due to COVID-19. Intensive Care Med. 50, 1685\u20131687. https:\/\/doi.org\/10.1007\/s00134-024-07554-w (2024).","journal-title":"Intensive Care Med."},{"key":"45319_CR9","doi-asserted-by":"publisher","first-page":"L9","DOI":"10.1152\/ajplung.00443.2022","volume":"325","author":"TA Lilien","year":"2023","unstructured":"Lilien, T. A., van Meenen, D. M. P., Schultz, M. J., Bos, L. D. J. & Bem, R. A. Hyperoxia-induced lung injury in acute respiratory distress syndrome: What is its relative impact?. Am. J. Physiol. Lung Cell. Mol. Physiol. 325, L9\u2013L16. https:\/\/doi.org\/10.1152\/ajplung.00443.2022 (2023).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"45319_CR10","doi-asserted-by":"publisher","first-page":"1568246","DOI":"10.3389\/fphar.2025.1568246","volume":"16","author":"X Zhou","year":"2025","unstructured":"Zhou, X., Tian, L., Xiong, W., Li, Y. & Liu, Q. Ferroptosis and hyperoxic lung injury: Insights into pathophysiology and treatment approaches. Front. Pharmacol. 16, 1568246. https:\/\/doi.org\/10.3389\/fphar.2025.1568246 (2025).","journal-title":"Front. Pharmacol."},{"key":"45319_CR11","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.3390\/antiox11122349","volume":"11","author":"A Tiboldi","year":"2022","unstructured":"Tiboldi, A. et al. Effects of hyperoxia and hyperoxic oscillations on the proteome of murine lung microvascular endothelium. Antioxidants 11, 2349. https:\/\/doi.org\/10.3390\/antiox11122349 (2022).","journal-title":"Antioxidants"},{"key":"45319_CR12","doi-asserted-by":"publisher","first-page":"3357","DOI":"10.1007\/s12033-023-00945-2","volume":"66","author":"Y Ren","year":"2024","unstructured":"Ren, Y. et al. Hyperoxia can induce lung injury by upregulating AECII autophagy and apoptosis via the mTOR pathway. Mol. Biotechnol. 66, 3357\u20133368. https:\/\/doi.org\/10.1007\/s12033-023-00945-2 (2024).","journal-title":"Mol. Biotechnol."},{"key":"45319_CR13","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3390\/ijms24010093","volume":"24","author":"I Psilopatis","year":"2023","unstructured":"Psilopatis, I. et al. EPH\/Ephrin targeting revolutionize lung cancer treatment?. Int. J. Mol. Sci. 24, 93. https:\/\/doi.org\/10.3390\/ijms24010093 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"45319_CR14","doi-asserted-by":"publisher","first-page":"397","DOI":"10.5056\/jnm19095","volume":"26","author":"Y Chen","year":"2020","unstructured":"Chen, Y. et al. EphrinA1\/EphA2 promotes epithelial hyperpermeability involving lipopolysaccharide-induced intestinal barrier dysfunction. J. Neurogastroenterol. Motil. 26, 397\u2013409. https:\/\/doi.org\/10.5056\/jnm19095 (2020).","journal-title":"J. Neurogastroenterol. Motil."},{"key":"45319_CR15","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1165\/rcmb.2011-0044OC","volume":"46","author":"TC Carpenter","year":"2012","unstructured":"Carpenter, T. C., Schroeder, W., Stenmark, K. R. & Schmidt, E. P. EphA2 promotes permeability and inflammatory responses to bleomycin-induced lung injury. Am. J. Respir. Cell Mol. Biol. 46, 40\u201347. https:\/\/doi.org\/10.1165\/rcmb.2011-0044OC (2012).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"45319_CR16","doi-asserted-by":"publisher","first-page":"L584","DOI":"10.1152\/ajplung.00073.2017","volume":"315","author":"RJ Good","year":"2018","unstructured":"Good, R. J. et al. MicroRNA dysregulation in lung injury: The role of the miR-26a\/EphA2 axis in regulation of endothelial permeability. Am. J. Physiol. Lung Cell. Mol. Physiol. 315, L584\u2013L594. https:\/\/doi.org\/10.1152\/ajplung.00073.2017 (2018).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"45319_CR17","doi-asserted-by":"publisher","first-page":"218","DOI":"10.4046\/trd.2015.78.3.218","volume":"78","author":"JY Hong","year":"2015","unstructured":"Hong, J. Y. et al. EphA2 receptor signaling mediates inflammatory responses in lipopolysaccharide-induced lung injury. Tuberc. Respir. Dis. 78, 218\u2013226. https:\/\/doi.org\/10.4046\/trd.2015.78.3.218 (2015).","journal-title":"Tuberc. Respir. Dis."},{"key":"45319_CR18","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.intimp.2019.04.008","volume":"72","author":"G Feng","year":"2019","unstructured":"Feng, G. et al. EphA2 antagonism alleviates LPS-induced acute lung injury via Nrf2\/HO-1, TLR4\/MyD88 and RhoA\/ROCK pathways. Int. Immunopharmacol. 72, 176\u2013185. https:\/\/doi.org\/10.1016\/j.intimp.2019.04.008 (2019).","journal-title":"Int. Immunopharmacol."},{"key":"45319_CR19","doi-asserted-by":"publisher","first-page":"3629","DOI":"10.3390\/ijms24043629","volume":"24","author":"JM Shin","year":"2023","unstructured":"Shin, J. M. et al. EphA1 and EphA2 signaling modulates epithelial permeability in human sinonasal epithelial cells, and rhinovirus infection induces epithelial barrier dysfunction via EphA2 receptor signaling. Int. J. Mol. Sci. 24, 3629. https:\/\/doi.org\/10.3390\/ijms24043629 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"45319_CR20","doi-asserted-by":"publisher","first-page":"111872","DOI":"10.1016\/j.isci.2025.111872","volume":"28","author":"R Fukuda","year":"2025","unstructured":"Fukuda, R., Beppu, S., Hinata, D., Kamada, Y. & Okiyoneda, T. Perturbation of EPHA2 and EFNA1 trans binding amplifies inflammatory response in airway epithelial cells. iScience 28, 111872. https:\/\/doi.org\/10.1016\/j.isci.2025.111872 (2025).","journal-title":"iScience"},{"key":"45319_CR21","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s12931-022-01992-0","volume":"23","author":"SH Lee","year":"2022","unstructured":"Lee, S. H. et al. NADPH oxidase 4 signaling in a ventilator-induced lung injury mouse model. Respir. Res. 23, 73. https:\/\/doi.org\/10.1186\/s12931-022-01992-0 (2022).","journal-title":"Respir. Res."},{"key":"45319_CR22","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1165\/rcmb.2017-0143OC","volume":"58","author":"BH Park","year":"2018","unstructured":"Park, B. H. et al. Erythropoietin-producing hepatoma receptor tyrosine kinase A2 modulation associates with protective effect of prone position in ventilator-induced lung injury. Am. J. Respir. Cell Mol. Biol. 58, 519\u2013529. https:\/\/doi.org\/10.1165\/rcmb.2017-0143OC (2018).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"45319_CR23","doi-asserted-by":"publisher","first-page":"331","DOI":"10.2353\/ajpath.2006.050435","volume":"168","author":"T Ojima","year":"2006","unstructured":"Ojima, T. et al. EphrinA1 inhibits vascular endothelial growth factor-induced intracellular signaling and suppresses retinal neovascularization and blood-retinal barrier breakdown. Am. J. Pathol. 168, 331\u2013339. https:\/\/doi.org\/10.2353\/ajpath.2006.050435 (2006).","journal-title":"Am. J. Pathol."},{"key":"45319_CR24","doi-asserted-by":"publisher","first-page":"L431","DOI":"10.1152\/ajplung.90256.2008","volume":"295","author":"J Larson","year":"2008","unstructured":"Larson, J., Schomberg, S., Schroeder, W. & Carpenter, T. C. Endothelial EphA receptor stimulation increases lung vascular permeability. Am. J. Physiol. Lung Cell. Mol. Physiol. 295, L431\u2013L439. https:\/\/doi.org\/10.1152\/ajplung.90256.2008 (2008).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"45319_CR25","doi-asserted-by":"publisher","first-page":"L856","DOI":"10.1152\/ajplung.00118.2009","volume":"297","author":"MA Cercone","year":"2009","unstructured":"Cercone, M. A., Schroeder, W., Schomberg, S. & Carpenter, T. C. EphA2 receptor mediates increased vascular permeability in lung injury due to viral infection and hypoxia. Am. J. Physiol. Lung Cell. Mol. Physiol. 297, L856\u2013L863. https:\/\/doi.org\/10.1152\/ajplung.00118.2009 (2009).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"45319_CR26","doi-asserted-by":"publisher","first-page":"e1008261","DOI":"10.1371\/journal.ppat.1008261","volume":"16","author":"TK Darling","year":"2020","unstructured":"Darling, T. K. et al. EphA2 contributes to disruption of the blood\u2013brain barrier in cerebral malaria. PLoS Pathog. 16, e1008261. https:\/\/doi.org\/10.1371\/journal.ppat.1008261 (2020).","journal-title":"PLoS Pathog."},{"key":"45319_CR27","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1038\/labinvest.3780195","volume":"80","author":"MA O\u2019Reilly","year":"2000","unstructured":"O\u2019Reilly, M. A. et al. Bcl-2 family gene expression during severe hyperoxia-induced lung injury. Lab. Invest. 80, 1845\u20131854. https:\/\/doi.org\/10.1038\/labinvest.3780195 (2000).","journal-title":"Lab. Invest."},{"key":"45319_CR28","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1165\/rcmb.2004-0141OC","volume":"31","author":"SV Truong","year":"2004","unstructured":"Truong, S. V. et al. Extracellular signal-regulated kinase activation delays hyperoxia-induced epithelial cell death under conditions of Akt downregulation. Am. J. Respir. Cell Mol. Biol. 31, 611\u2013618. https:\/\/doi.org\/10.1165\/rcmb.2004-0141OC (2004).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"45319_CR29","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.ccr.2009.04.009","volume":"16","author":"H Miao","year":"2009","unstructured":"Miao, H. et al. EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt. Cancer Cell 16, 9\u201320. https:\/\/doi.org\/10.1016\/j.ccr.2009.04.009 (2009).","journal-title":"Cancer Cell"},{"key":"45319_CR30","doi-asserted-by":"publisher","first-page":"597942","DOI":"10.3389\/fphar.2020.597942","volume":"11","author":"S Sidramagowda Patil","year":"2021","unstructured":"Sidramagowda Patil, S. et al. Alda-1 attenuates hyperoxia-induced acute lung injury in mice. Front. Pharmacol. 11, 597942. https:\/\/doi.org\/10.3389\/fphar.2020.597942 (2021).","journal-title":"Front. Pharmacol."},{"key":"45319_CR31","doi-asserted-by":"publisher","first-page":"41508","DOI":"10.18632\/oncotarget.6131","volume":"6","author":"L Galam","year":"2015","unstructured":"Galam, L., Failla, A., Soundararajan, R., Lockey, R. F. & Kolliputi, N. 4-Hydroxynonenal regulates mitochondrial function in human small airway epithelial cells. Oncotarget 6, 41508\u201341521. https:\/\/doi.org\/10.18632\/oncotarget.6131 (2015).","journal-title":"Oncotarget"},{"key":"45319_CR32","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1152\/japplphysiol.00892.2003","volume":"96","author":"JB Dean","year":"2004","unstructured":"Dean, J. B., Mulkey, D. K., Henderson, R. A., Potter, S. J. & Putnam, R. W. Hyperoxia, reactive oxygen species, and hyperventilation: Oxygen sensitivity of brain stem neurons. J. Appl. Physiol. 96, 784\u2013791. https:\/\/doi.org\/10.1152\/japplphysiol.00892.2003 (2004).","journal-title":"J. Appl. Physiol."},{"key":"45319_CR33","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1164\/rccm.200902-0296OC","volume":"180","author":"SM Carnesecchi","year":"2009","unstructured":"Carnesecchi, S. M. et al. NADPH oxidase-1 plays a crucial role in hyperoxia-induced acute lung injury in mice. Am. J. Respir. Crit. Care Med. 180, 972\u2013981. https:\/\/doi.org\/10.1164\/rccm.200902-0296OC (2009).","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45319-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45319-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45319-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:53:04Z","timestamp":1778626384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45319-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["45319"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-45319-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"assertion":[{"value":"4 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All animal procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC-2013-0307) of the Yonsei University College of Medicine (Seoul, South Korea) and were conducted in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals. Male wild-type C57BL\/6\u00a0J mice (8\u201310\u00a0weeks old, 20\u201324\u00a0g; Orient Bio, Seongnam, South Korea) were housed under controlled temperature and a 12\u00a0h\u201312\u00a0h light\u2013dark cycle with free access to standard chow and water. All mice were specific pathogen-free and acclimatized for at least 7\u00a0days before experimentation. No prespecified exclusion criteria were applied, and no animals were excluded from the analyses. Mice were euthanized by intraperitoneal injection of a lethal dose (2\u20133 times the standard anesthetic dose) of Zoletil (30\u00a0mg\/kg) and xylazine (Rompun, 10\u00a0mg\/kg), after which bronchoalveolar lavage fluid and lung tissue were collected. The study is reported in accordance with the ARRIVE 2.0 guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"14905"}}