{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T10:27:42Z","timestamp":1763202462319},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP\u2010111054","PJT153406","PJT166004"],"award-info":[{"award-number":["MOP\u2010111054","PJT153406","PJT166004"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102016\u201004378"],"award-info":[{"award-number":["RGPIN\u20102016\u201004378"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>How does the downregulation of ENaC, the major driving force for alveolar fluid clearance, impact acute lung injury outcomes induced by bleomycin, featuring alveolar damage, as observed during ARDS exudative phase?<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>ENaC downregulation in \u03b1ENaC(\u2212\/\u2212)Tg+ mice did not elicit a substantial worsening impact on the main bleomycin outcomes. In ARDS patients, both ENaC alteration and alveolar damage are observed. Thus, novel therapeutic avenues, favouring alveolar integrity restauration, in addition to lung oedema resolution capacity, mainly driven by ENaC, would be essential.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The exudative phase of acute respiratory distress syndrome (ARDS) is characterized by extended alveolar damage, resulting in accumulation of protein\u2010rich inflammatory oedematous fluid in the alveolar space. Na<jats:sup>+<\/jats:sup> reabsorption through ENaC channels is a major driving force for alveolar fluid clearance (AFC) in physiological and pathological conditions. It has previously been shown that partial \u03b1ENaC impairment in transgenic (\u03b1ENaC(\u2212\/\u2212)Tg+) mice results in reduced AFC in basal conditions and increased wet\/dry ratio after thiourea\u2010induced lung oedema, a model in which the integrity of the alveolar epithelium is preserved. The goal of this study was to further investigate the impact of \u03b1ENaC downregulation in \u03b1ENaC(\u2212\/\u2212)Tg+ mice using an experimental model of acute lung injury induced by bleomycin. A non\u2010significant trend in enhanced weight loss and mortality rates was observed after the bleomycin challenge in \u03b1ENaC(\u2212\/\u2212)Tg+ compared to wild\u2010type (WT) mice. Bronchoalveolar lavage analyses revealed increased TNF\u03b1 levels and protein concentrations, as indexes of lung inflammation and alveolar damage, in \u03b1ENaC(\u2212\/\u2212)Tg+ mice, compared to WT, at day 3 post\u2010bleomycin, although a statistical difference was no longer measured at day 7. Differential immune cell counts were similar in WT and \u03b1ENaC(\u2212\/\u2212)Tg+ mice challenged with bleomycin. Moreover, lung weight measurements indicated similar oedema levels in WT mice and in transgenic mice with impaired ENaC channels. Altogether, our data indicated that change in ENaC expression does not elicit a significant impact on lung oedema level\/resolution in the bleomycin model, featuring alveolar damage.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep089060","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T13:05:49Z","timestamp":1611752749000},"page":"1110-1119","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of ENaC downregulation in transgenic mice on the outcomes of acute lung injury induced by bleomycin"],"prefix":"10.1113","volume":"106","author":[{"given":"M\u00e9lissa","family":"Aubin Vega","sequence":"first","affiliation":[{"name":"Centre de recherche du Centre hospitalier de l'Universit\u00e9 de Montr\u00e9al (CRCHUM)  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"D\u00e9partement de M\u00e9decine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9cile","family":"Chupin","sequence":"additional","affiliation":[{"name":"Centre de recherche du Centre hospitalier de l'Universit\u00e9 de Montr\u00e9al (CRCHUM)  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"D\u00e9partement de M\u00e9decine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Mass\u00e9","sequence":"additional","affiliation":[{"name":"Centre de recherche du Centre hospitalier de l'Universit\u00e9 de Montr\u00e9al (CRCHUM)  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Institut de recherches cliniques de Montr\u00e9al (IRCM)  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Dagenais","sequence":"additional","affiliation":[{"name":"Centre de recherche du Centre hospitalier de l'Universit\u00e9 de Montr\u00e9al (CRCHUM)  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Institut de recherches cliniques de Montr\u00e9al (IRCM)  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yves","family":"Berthiaume","sequence":"additional","affiliation":[{"name":"Centre de recherche du Centre hospitalier de l'Universit\u00e9 de Montr\u00e9al (CRCHUM)  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"D\u00e9partement de M\u00e9decine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Institut de recherches cliniques de Montr\u00e9al (IRCM)  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuelle","family":"Brochiero","sequence":"additional","affiliation":[{"name":"Centre de recherche du Centre hospitalier de l'Universit\u00e9 de Montr\u00e9al (CRCHUM)  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"D\u00e9partement de M\u00e9decine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,2,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00076.2007"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623315598399"},{"key":"e_1_2_9_4_1","first-page":"37","volume-title":"Lung Biology in Health and Disease","author":"Albertine K. 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