{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T22:12:14Z","timestamp":1788214334470,"version":"build-2803163510"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Clinical Research Project of Shanghai Municipal Health Commission","award":["202140100"],"award-info":[{"award-number":["202140100"]}]},{"name":"Health Science and Technology Project of Pudong New Area Health Commission","award":["PW2023A-33"],"award-info":[{"award-number":["PW2023A-33"]}]},{"name":"Minsheng Research Project of Pudong New Area Science and Technology Development Fund","award":["PKJ2022-Y39"],"award-info":[{"award-number":["PKJ2022-Y39"]}]},{"name":"Medical Discipline Construction Project of Pudong Health Committee of Shanghai","award":["PWYts2021-18"],"award-info":[{"award-number":["PWYts2021-18"]}]},{"name":"Reserve Discipline Platform Construction Project of Fudan University affiliated Jinshan Hospital \u2013 Neurosurgery","award":["HBXK-2022-4"],"award-info":[{"award-number":["HBXK-2022-4"]}]},{"name":"Key Medical Specialty Construction Project of Jinshan District","award":["JSZK2023B01"],"award-info":[{"award-number":["JSZK2023B01"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Acute respiratory distress syndrome (ARDS) \/ acute lung injury (ALI) is a serious medical disease characterized by pulmonary dysfunction and inflammation. This study aims to determine the main molecular modules linked to ARDS and investigate the role of Fibulin-1 (FBLN1) in regulating ferroptosis in ARDS.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Weighted Gene Co-expression Network Analysis (WGCNA) was employed on the GSE263867 dataset to find key modules associated with ALI. Differentially expressed genes (DEGs) and protein-protein interaction (PPI) networks were analyzed. MLE-12 cells were treated with lipopolysaccharide (LPS) to induce ferroptosis. <jats:italic>In vitro<\/jats:italic> studies were conducted to investigate the effects of FBLN1 and Transforming Growth Factor Beta 1 (TGF-\u03b2) overexpression on cell viability, oxidative stress markers, and ferroptosis-related proteins.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>WGCNA identified the turquoise module as significantly negatively correlated with ARDS. Five key overlapping genes (<jats:italic>GRIA1<\/jats:italic>, <jats:italic>OGN<\/jats:italic>, <jats:italic>COL14A1<\/jats:italic>, <jats:italic>FBLN1<\/jats:italic>, and <jats:italic>COL6A3<\/jats:italic>) were significantly downregulated in ARDS samples. LPS treatment induced ferroptosis in MLE-12 cells, indicated by increased malondialdehyde (MDA), lipid reactive oxygen species (ROS), and ferrous iron (Fe<jats:sup>2<\/jats:sup>\u207a) levels, and decreased cell viability and glutathione (GSH) levels. FBLN1 overexpression partially reversed these effects. Additionally, FBLN1 inhibited the TGF-\u03b2\/Smad signaling pathway, as shown by decreased TGF-\u03b2 and p-Smad protein levels. TGF-\u03b2 overexpression exacerbated LPS-induced oxidative stress and ferroptosis, reducing cell viability and GSH levels. FBLN1 overexpression counteracted this effect, suggesting antagonistic roles for FBLN1 and TGF-\u03b2 in regulating ferroptosis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study highlights <jats:italic>FBLN1<\/jats:italic> as a critical regulator of ferroptosis in ARDS. Targeting the TGF-\u03b2\/Smad pathway to modulate <jats:italic>FBLN1<\/jats:italic> expression offers a potential therapeutic strategy to alleviate oxidative stress and mitigate pulmonary injury in inflammatory lung diseases.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0314750","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T18:32:07Z","timestamp":1734114727000},"page":"e0314750","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["FBLN1 regulates ferroptosis in acute respiratory distress syndrome by reducing free ferrous iron by inhibiting the TGF-\u03b2\/Smad pathway"],"prefix":"10.1371","volume":"19","author":[{"given":"Yaping","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youbo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchao","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7753-8628","authenticated-orcid":true,"given":"Haihan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,13]]},"reference":[{"issue":"6","key":"pone.0314750.ref001","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.rcl.2022.06.005","article-title":"Pathogenesis, imaging, and evolution of acute lung injury","volume":"60","author":"S. 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