{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:36:46Z","timestamp":1791491806327,"version":"4.3.4"},"reference-count":46,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"709","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,8,16]]},"abstract":"<jats:p>\n                    Aging is a major risk factor of high incidence and increased mortality of acute respiratory distress syndrome (ARDS). Here, we demonstrated that persistent lung injury and high mortality in aged mice after sepsis challenge were attributable to impaired endothelial regeneration and vascular repair. Genetic lineage tracing study showed that endothelial regeneration after sepsis-induced vascular injury was mediated by lung resident endothelial proliferation in young adult mice, whereas this intrinsic regenerative program was impaired in aged mice. Expression of forkhead box M1 (FoxM1), an important mediator of endothelial regeneration in young mice, was not induced in lungs of aged mice. Transgenic\n                    <jats:italic>FOXM1<\/jats:italic>\n                    expression or in vivo endothelium-targeted nanoparticle delivery of the\n                    <jats:italic>FOXM1<\/jats:italic>\n                    gene driven by an endothelial cell (EC)\u2013specific promoter reactivated endothelial regeneration, normalized vascular repair and resolution of inflammation, and promoted survival in aged mice after sepsis challenge. In addition, treatment with the FDA-approved DNA demethylating agent decitabine was sufficient to reactivate FoxM1-dependent endothelial regeneration in aged mice, reverse aging-impaired resolution of inflammatory injury, and promote survival. Mechanistically, aging-induced\n                    <jats:italic>Foxm1<\/jats:italic>\n                    promoter hypermethylation in mice, which could be inhibited by decitabine treatment, inhibited\n                    <jats:italic>Foxm1<\/jats:italic>\n                    induction after sepsis challenge. In COVID-19 lung autopsy samples,\n                    <jats:italic>FOXM1<\/jats:italic>\n                    was not induced in vascular ECs of elderly patients in their 80s, in contrast with middle-aged patients (aged 50 to 60 years). Thus, reactivation of FoxM1-mediated endothelial regeneration and vascular repair may represent a potential therapy for elderly patients with ARDS.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.abm5755","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T13:58:41Z","timestamp":1692194321000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":69,"title":["Endothelial FoxM1 reactivates aging-impaired endothelial regeneration for vascular repair and resolution of inflammatory lung injury"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4536-3847","authenticated-orcid":true,"given":"Xiaojia","family":"Huang","sequence":"first","affiliation":[{"name":"Program for Lung and Vascular Biology and Section for Injury Repair and Regeneration Research, Stanley Manne Children\u2019s Research Institute, Ann &amp; Robert H.\u00a0Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA."},{"name":"Department of Pediatrics, Division of Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1175-7109","authenticated-orcid":true,"given":"Xianming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Program for Lung and Vascular Biology and Section for Injury Repair and Regeneration Research, Stanley Manne Children\u2019s Research Institute, Ann &amp; Robert H.\u00a0Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA."},{"name":"Department of Pediatrics, Division of Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narsa","family":"Machireddy","sequence":"additional","affiliation":[{"name":"Program for Lung and Vascular Biology and Section for Injury Repair and Regeneration Research, Stanley Manne Children\u2019s Research Institute, Ann &amp; Robert H.\u00a0Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA."},{"name":"Department of Pediatrics, Division of Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin E.","family":"Evans","sequence":"additional","affiliation":[{"name":"Program for Lung and Vascular Biology and Section for Injury Repair and Regeneration Research, Stanley Manne Children\u2019s Research Institute, Ann &amp; Robert H.\u00a0Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA."},{"name":"Department of Pediatrics, Division of Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7037-4660","authenticated-orcid":true,"given":"Shawn 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4597-3095","authenticated-orcid":true,"given":"Yun","family":"Fang","sequence":"additional","affiliation":[{"name":"Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2056-612X","authenticated-orcid":true,"given":"G\u00f6khan M.","family":"Mutlu","sequence":"additional","affiliation":[{"name":"Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3162-3238","authenticated-orcid":true,"given":"David","family":"Wu","sequence":"additional","affiliation":[{"name":"Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 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