{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:22:37Z","timestamp":1787595757557,"version":"build-2736575974"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["FDM202006011412"],"award-info":[{"award-number":["FDM202006011412"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Premature infants frequently require oxygen supplementation due to lung immaturity, exposing them to the risk of bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by arrested alveolar growth and inflammation. Connexin 43-dependent gap junctions (Cx43-GJ) regulate intercellular communication during lung development and inflammatory responses, but their involvement in BPD remains incompletely defined. This study aimed to assess the contribution of Cx43-GJ in experimental BPD and to evaluate whether selective pharmacological inhibition of Cx43 modulates hyperoxia-induced lung injury and pulmonary hypertension. Newborn rats were exposed to normoxia or hyperoxia (90% O\n                    <jats:sub>2<\/jats:sub>\n                    ) for 14 days and treated daily with the Cx43-GJ inhibitor\n                    <jats:sup>43<\/jats:sup>\n                    Gap26 or vehicle. Human fetal pulmonary artery smooth muscle cells (HfPA-SMC) were exposed to 21% O\n                    <jats:sub>2<\/jats:sub>\n                    or 60% O\n                    <jats:sub>2<\/jats:sub>\n                    and treated with or without\n                    <jats:sup>43<\/jats:sup>\n                    Gap26 for 48 hours. Lung morphology, function, surfactant protein expression, extracellular matrix markers, macrophage phenotype, cytokine secretion, and oxidative stress markers were assessed.\n                    <jats:italic>In vivo<\/jats:italic>\n                    ,\n                    <jats:sup>43<\/jats:sup>\n                    Gap26 reduced hyperoxia-induced Cx43 overexpression and partially improved alveolarization. However,\n                    <jats:sup>43<\/jats:sup>\n                    Gap26 failed to prevent alterations in lung function, decreased surfactant protein-B expression, extracellular matrix remodeling, macrophage M2 polarization, increased tissue inhibitor of metalloproteinase-1 secretion, pulmonary hypertension, or mortality. Inhibition of Cx43 was also associated with reduced markers of type II alveolar epithelial cell expression. In HfPA-SMC,\n                    <jats:sup>43<\/jats:sup>\n                    Gap26 did not modify hyperoxia-induced secretion of pro-inflammatory cytokines, despite increased Cx43 expression. Classical markers of oxidative damage were not significantly increased under our experimental conditions, although heme oxygenase-1 expression was elevated. Overall, pharmacological inhibition of Cx43 partially restored alveolar structure but did not prevent major pathological features of experimental BPD or pulmonary hypertension. These findings suggest that Cx43-GJ signaling is involved in the regulation of alveolar structure during hyperoxic lung injury, but its pharmacological inhibition alone is insufficient to prevent the complex structural and vascular alterations characteristic of experimental BPD.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0356364","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:24:25Z","timestamp":1787592265000},"page":"e0356364","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of connexin 43 in hyperoxia-induced bronchopulmonary dysplasia and associated pulmonary hypertension"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6023-0772","authenticated-orcid":true,"given":"Claire-Marie","family":"Pilard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Gassiat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Cardouat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Gauthereau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Robillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Dumas-de-la-Roque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Sauvestre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Pelluard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Berenguer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melie","family":"Sarreau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Sentilhes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9deric","family":"Coatleven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Vincienne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Marthan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Freund-Michel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Guibert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"issue":"7","key":"pone.0356364.ref001","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1056\/NEJM196702162760701","article-title":"Pulmonary disease following respirator therapy of hyaline-membrane disease. 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