{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:18:17Z","timestamp":1788805097765,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,3,30]],"date-time":"2016-03-30T00:00:00Z","timestamp":1459296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (<jats:styled-content style=\"fixed-case\">HALI<\/jats:styled-content>), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in <jats:styled-content style=\"fixed-case\">HALI<\/jats:styled-content> are poorly understood. <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010D in pathological oedema was unknown. To address these issues, we exposed <jats:italic>Vegfd<\/jats:italic>\u2010deficient mice to hyperoxia. The resulting pulmonary oedema in <jats:italic>Vegfd<\/jats:italic>\u2010deficient mice was substantially reduced compared to wild\u2010type, as was the protein content of bronchoalveolar lavage fluid, consistent with reduced vascular leak. Vegf\u2010d and its receptor Vegfr\u20103 were more highly expressed in lungs of hyperoxic, versus normoxic, wild\u2010type mice, indicating that components of the Vegf\u2010d signalling pathway are up\u2010regulated in hyperoxia. Importantly, <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010D and its receptors were co\u2010localized on blood vessels in clinical samples of human lungs exposed to hyperoxia; hence, <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010D may act directly on blood vessels to promote fluid leak. Our studies show that Vegf\u2010d promotes oedema in response to hyperoxia in mice and support the hypothesis that <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010D signalling promotes vascular leak in human <jats:styled-content style=\"fixed-case\">HALI<\/jats:styled-content>. \u00a9 2016 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.4708","type":"journal-article","created":{"date-parts":[[2016,2,29]],"date-time":"2016-02-29T01:03:23Z","timestamp":1456707803000},"page":"152-161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["VEGF\u2010D promotes pulmonary oedema in hyperoxic acute lung injury"],"prefix":"10.1002","volume":"239","author":[{"given":"Teruhiko","family":"Sato","sequence":"first","affiliation":[{"name":"Peter MacCallum 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