{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:51:25Z","timestamp":1793501485692,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Acute lung injury (ALI) is a common and severe complication of sepsis with a high mortality rate. Ferroptosis, an iron\u2010dependent form of cell death, contributes to lung injury. Homeobox A5 (HOXA5) is involved in the regulation of septic acute kidney damage; however, its function on ferroptosis in septic ALI remains unclear. An in vitro model of septic lung injury was established in the pulmonary epithelial cell line (MLE\u201012) via lipopolysaccharide (LPS) stimulation. Cell viability, ferrous iron (Fe\n                    <jats:sup>2+<\/jats:sup>\n                    ) level, and cellular lipid reactive oxygen species (ROS) were determined with Cell Counting Kit\u20108 assay, iron assay kit, and BODIPY\u2122 665\/676 molecular probe, respectively. HOXA5, ferroptosis suppressor protein 1 (FSP1), sirtuin 5 (SIRT5), and glutathione peroxidase 4 (GPX4) expressions were measured using western blotting and Real\u2010Time Quantitative Polymerase Chain Reaction (RT\u2010qPCR. Chromatin immunoprecipitation and luciferase reporter assays were performed to validate HOXA5 binding to the FSP1\/GPX4 promoter, and regulation of SIRT5 on HOXA5 desuccinylation was confirmed through co\u2010immunoprecipitation. LPS stimulation induced ferroptosis (reduced cell viability, elevated Fe\n                    <jats:sup>2+<\/jats:sup>\n                    and lipid ROS levels, and decreased GPX4 levels) and downregulated FSP1 and HOXA5 protein levels.\n                    <jats:italic>HOXA5<\/jats:italic>\n                    overexpression neutralized LPS\u2010induced ferroptosis. Moreover, LPS exposure inhibited HOXA5 binding to the\n                    <jats:italic>FSP1<\/jats:italic>\n                    promoter, which was counteracted via\n                    <jats:italic>HOXA5<\/jats:italic>\n                    overexpression. Furthermore, SIRT5 overexpression suppressed LPS\u2010induced ferroptosis. In LPS\u2010challenged MLE\u201012 cells, SIRT5\u2010mediated HOXA5 desuccinylation was reduced.\n                    <jats:italic>HOXA5<\/jats:italic>\n                    depletion neutralized the suppressive role of\n                    <jats:italic>SIRT5<\/jats:italic>\n                    overexpression in LPS\u2010induced ferroptosis. SIRT5\u2010mediated HOXA5 desuccinylation inhibited LPS\u2010induced ferroptosis by upregulating FSP1, which may offer a prospective therapeutic strategy for septic lung injury.\n                  <\/jats:p>","DOI":"10.1002\/kjm2.12921","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T07:09:48Z","timestamp":1734937788000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<scp>SIRT5<\/scp>\n                    \u2010mediated\n                    <scp>HOXA5<\/scp>\n                    desuccinylation inhibits ferroptosis to alleviate sepsis induced\u2010lung injury"],"prefix":"10.1002","volume":"41","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Ningbo University  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Ningbo University  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Ningbo University  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3410-2879","authenticated-orcid":false,"given":"Ji\u2010Hui","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Ningbo University  Ningbo Zhejiang 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