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Quebec","award":["PJT166004"],"award-info":[{"award-number":["PJT166004"]}]},{"name":"AIRS network","award":["RGPIN-2016-04378"],"award-info":[{"award-number":["RGPIN-2016-04378"]}]},{"name":"AIRS network","award":["RGPIN-2023-04496"],"award-info":[{"award-number":["RGPIN-2023-04496"]}]},{"name":"AIRS network","award":["MOP-111054"],"award-info":[{"award-number":["MOP-111054"]}]},{"name":"AIRS network","award":["PJT153406"],"award-info":[{"award-number":["PJT153406"]}]},{"name":"AIRS network","award":["PJT166004"],"award-info":[{"award-number":["PJT166004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute Respiratory Distress Syndrome (ARDS) is a complex and devastating form of respiratory failure, with high mortality rates, for which there is no pharmacological treatment. The acute exudative phase of ARDS is characterized by severe damage to the alveolar\u2013capillary barrier, infiltration of protein-rich fluid into the lungs, neutrophil recruitment, and high levels of inflammatory mediators. Rapid resolution of this reversible acute phase, with efficient restoration of alveolar functional integrity, is essential before the establishment of irreversible fibrosis and respiratory failure. Several lines of in vitro and in vivo evidence support the involvement of potassium (K+) channels\u2014particularly KvLQT1, expressed in alveolar cells\u2014in key cellular mechanisms for ARDS resolution, by promoting alveolar fluid clearance and epithelial repair processes. The aim of our study was to investigate whether pharmacological activation of KvLQT1 channels could elicit beneficial effects on ARDS parameters in an animal model of acute lung injury. We used the well-established bleomycin model, which mimics (at day 7) the key features of the exudative phase of ARDS. Our data demonstrate that treatments with the KvLQT1 activator R-L3, delivered to the lungs, failed to improve endothelial permeability and lung edema in bleomycin mice. However, KvLQT1 activation significantly reduced neutrophil recruitment and tended to decrease levels of pro-inflammatory cytokines\/chemokines in bronchoalveolar lavages after bleomycin administration. Importantly, R-L3 treatment was associated with significantly lower injury scores, higher levels of alveolar type I (HTI-56, AQP5) and II (pro-SPC) cell markers, and improved alveolar epithelial repair capacity in the presence of bleomycin. Together, these results suggest that the KvLQT1 K+ channel may be a potential target for the resolution of the acute phase of ARDS.<\/jats:p>","DOI":"10.3390\/ijms26157632","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T08:33:06Z","timestamp":1754555586000},"page":"7632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pro-Reparative Effects of KvLQT1 Potassium Channel Activation in a Mouse Model of Acute Lung Injury Induced by Bleomycin"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6846-9110","authenticated-orcid":false,"given":"Tom","family":"Voisin","sequence":"first","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5478-9340","authenticated-orcid":false,"given":"Alban","family":"Girault","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiologie Cellulaire et Mol\u00e9culaire (LPCM UR UPJV 4667), 80039 Amiens Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lissa","family":"Aubin Vega","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9milie","family":"Meunier","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Chebli","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anik","family":"Priv\u00e9","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, QC H2X 0A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3665-2652","authenticated-orcid":false,"given":"Damien","family":"Adam","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8182-943X","authenticated-orcid":false,"given":"Emmanuelle","family":"Brochiero","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1001\/jama.2016.0291","article-title":"Epidemiology, Patterns of Care, and Mortality for Patients with Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries","volume":"315","author":"Bellani","year":"2016","journal-title":"JAMA\u2014J. 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