{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:04:03Z","timestamp":1771463043254,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the effects of localized subglottic knockout of E\u2010cadherin (<jats:italic>CDH1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) on survival, tracheal luminal thickness, and fibrotic gene expression in a mouse model of subglottic stenosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Case\u2010control in vivo mouse study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Tertiary care academic hospital.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice with loxP sites flanking E\u2010cadherin underwent extratracheal placement of a fibrin\u2010plasmin gel embedded with either CRE\u2010expressing or control adenovirus. Mice then underwent chemomechanical injury to induce laryngotracheal stenosis, with harvest of subglottis\/tracheas 21 days later. Immunofluorescence and Western blotting were used to confirm E\u2010cadherin knockout. Outcomes of interest included Kaplan\u2010Meier survival curves (n\u2009=\u200940), lamina propria thickness on hematoxylin\u2010eosin (H&amp;E) histology (n\u2009=\u20098), and fibrotic gene expression (n\u2009=\u20093).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immunofluorescence and Western blotting confirmed decreased E\u2010cadherin expression in <jats:italic>CDH1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>. On H&amp;E, lamina propria thickness was greater in <jats:italic>CDH1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice (mean difference [95% CI] in \u03bcm, 107.2 [74.8\u2010139.7], <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). Survival was significantly shorter for knockout mice relative to control (median survival in days, 5.0 vs 8.5; <jats:italic>P<\/jats:italic>\u2009=\u2009.007). Further, fibrotic gene expression of <jats:italic>COL1<\/jats:italic> (mean difference [95% CI] in log\u2010fold change, 11.5 [1.9\u201021.0]; <jats:italic>P<\/jats:italic>\u2009=\u2009.03), <jats:italic>COL3<\/jats:italic> (31.0 [11.5\u201050.5]; <jats:italic>P<\/jats:italic>\u2009=\u2009.01), <jats:italic>COL5<\/jats:italic> (6.8 [3.1\u201010.4]; <jats:italic>P<\/jats:italic>\u2009=\u2009.007), and <jats:italic>FN1<\/jats:italic> (6.9 [1.3\u201012.6]; <jats:italic>P<\/jats:italic>\u2009=\u2009.03) was significantly greater relative to control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>CDH1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> results in greater fibrosis and increased mortality, further supporting the role of epithelial barrier dysfunction in the pathogenesis of subglottic stenosis. Therapies that restore epithelial integrity may therefore represent a rational pharmacologic target.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ohn.1226","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T10:04:46Z","timestamp":1742378686000},"page":"2003-2008","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Localized Knockout of E\u2010Cadherin in Subglottic Mucosa Increases Fibrosis"],"prefix":"10.1002","volume":"172","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1004-7606","authenticated-orcid":false,"given":"Raymond J.","family":"So","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel L.","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head 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