{"doi":"10.1002/ohn.1226","title":"Localized Knockout of E‐Cadherin in Subglottic Mucosa Increases Fibrosis","abstract":"OBJECTIVE: ) on survival, tracheal luminal thickness, and fibrotic gene expression in a mouse model of subglottic stenosis. STUDY DESIGN: Case-control in vivo mouse study. SETTING: Tertiary care academic hospital. METHODS: Mice with loxP sites flanking E-cadherin underwent extratracheal placement of a fibrin-plasmin gel embedded with either CRE-expressing 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-cadherin knockout. Outcomes of interest included Kaplan-Meier survival curves (n = 40), lamina propria thickness on hematoxylin-eosin (H&E) histology (n = 8), and fibrotic gene expression (n = 3). RESULTS: mice (mean difference [95% CI] in μm, 107.2 [74.8-139.7], P < .001). Survival was significantly shorter for knockout mice relative to control (median survival in days, 5.0 vs 8.5; P = .007). Further, fibrotic gene expression of COL1 (mean difference [95% CI] in log-fold change, 11.5 [1.9-21.0]; P = .03), COL3 (31.0 [11.5-50.5]; P = .01), COL5 (6.8 [3.1-10.4]; P = .007), and FN1 (6.9 [1.3-12.6]; P = .03) was significantly greater relative to control. CONCLUSION: 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.","journal":"Otolaryngology","year":2025,"id":550327,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":642564,"name":"Samuel L. Collins","orcid":"0000-0002-0292-6937","position":1,"is_corresponding":false},{"id":229835,"name":"Yee Chan‐Li","orcid":null,"position":2,"is_corresponding":false},{"id":381363,"name":"Ioan Lina","orcid":"0000-0002-8619-7312","position":3,"is_corresponding":false},{"id":381368,"name":"Alexander Gelbard","orcid":"0000-0003-0078-1305","position":4,"is_corresponding":false},{"id":381366,"name":"Kevin Motz","orcid":"0000-0002-9255-7265","position":5,"is_corresponding":false},{"id":240456,"name":"Alexander T. Hillel","orcid":"0000-0001-8471-5449","position":6,"is_corresponding":false},{"id":1011463,"name":"Raymond J. So","orcid":"0000-0003-1004-7606","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T02:54:16.596730Z","pmid":"40105452","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}