{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:32:16Z","timestamp":1768505536267,"version":"3.49.0"},"posted":{"date-parts":[[2023,3,15]]},"group-title":"Pathology","reference-count":52,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Hyperoxia-induced inflammation contributes significantly to developmental lung injury and bronchopulmonary dysplasia (BPD) in preterm infants. Platelet activating factor (PAF) is known to be a major driver of inflammation in lung diseases such as asthma and pulmonary fibrosis, but its role in BPD has not been previously investigated. Therefore, to determine whether PAF signaling independently modulates neonatal hyperoxic lung injury and BPD pathogenesis, lung structure was assessed in 14 day-old C57BL\/6 wild-type (WT) and PAF receptor knockout (PTAFR KO) mice that were exposed to 21% (normoxia) or 85% O\n                  <jats:sub>2<\/jats:sub>\n                  (hyperoxia) from postnatal day 4. Lung morphometry showed that PTAFR KO mice had attenuated hyperoxia-induced alveolar simplification when compared to WT mice. Functional analysis of gene expression data from hyperoxia-exposed vs. normoxia-exposed lungs of WT and PTAFR KO showed that the most upregulated pathways were the\n                  <jats:italic>hypercytokinemia\/hyperchemokinemia<\/jats:italic>\n                  pathway in WT mice,\n                  <jats:italic>NAD signaling<\/jats:italic>\n                  pathway in PTAFR KO mice, and\n                  <jats:italic>agranulocyte adhesion and diapedesis<\/jats:italic>\n                  as well as other pro-fibrotic pathways such as\n                  <jats:italic>tumor microenvironment<\/jats:italic>\n                  and\n                  <jats:italic>oncostatin-M signaling<\/jats:italic>\n                  in both mice strains, indicating that PAF signaling may contribute to inflammation but may not be a significant mediator of fibrotic processes during hyperoxic neonatal lung injury. Gene expression analysis also indicated increased expression of pro-inflammatory genes such as CXCL1, CCL2 and IL-6 in the lungs of hyperoxia-exposed WT mice and metabolic regulators such as HMGCS2 and SIRT3 in the lungs of PTAFR KO mice, suggesting that PAF signaling may modulate BPD risk through changes in pulmonary inflammation and\/or metabolic reprogramming in preterm infants.\n                <\/jats:p>","DOI":"10.1101\/2023.03.14.532697","type":"posted-content","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T13:20:17Z","timestamp":1678886417000},"source":"Crossref","is-referenced-by-count":0,"title":["Platelet Activating Factor Activity Modulates Hyperoxic Neonatal Lung Injury Severity"],"prefix":"10.64898","author":[{"given":"Aaron J.","family":"Yee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jegen","family":"Kandasamy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namasivayam","family":"Ambalavanan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changchun","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Halloran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelida","family":"Olave","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teodora","family":"Nicola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamas","family":"Jilling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023031805351500000_2023.03.14.532697v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2017.10.014"},{"key":"2023031805351500000_2023.03.14.532697v1.2","doi-asserted-by":"crossref","unstructured":"Balany J , Bhandari V . 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