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Previous studies implicated the nicotinamide adenine dinucleotide phosphate\u2013reduced oxidase dual oxidase\u20131 (DUOX1) in redox signaling pathways involved in in vitro epithelial wound responses to infection and injury. However, the importance of epithelial DUOX1 in in vivo epithelial repair pathways has not been established. Using small interfering (si)RNA silencing of DUOX1 expression, we show the critical importance of DUOX1 in wound responses in murine tracheal epithelial (MTE) cells in vitro, as well as its contribution to epithelial regeneration in vivo in a murine model of epithelial injury induced by naphthalene, a selective toxicant of nonciliated respiratory epithelial cells (club cells [Clara]). Whereas naphthalene-induced club-cell injury is normally followed by epithelial regeneration after 7 and 14 days, such airway reepithelialization was significantly delayed after the silencing of airway DUOX1 by oropharyngeal administration of DUOX1-targeted siRNA. Wound closure in MTE cells was related to DUOX1-dependent activation of the epidermal growth factor receptor (EGFR) and the transcription factor signal transducer and activator of transcription\u20133 (STAT3), known mediators of epithelial cell migration and wound responses. Moreover, in vivo DUOX1 silencing significantly suppressed naphthalene-induced activation of STAT3 and EGFR during early stages of epithelial repair. In conclusion, these experiments demonstrate for the first time an important function for epithelial DUOX1 in lung epithelial regeneration in vivo, by promoting EGFR\u2013STAT3 signaling and cell migration as critical events in initial repair.<\/jats:p>","DOI":"10.1165\/rcmb.2012-0393oc","type":"journal-article","created":{"date-parts":[[2012,12,14]],"date-time":"2012-12-14T02:17:11Z","timestamp":1355451431000},"page":"337-345","source":"Crossref","is-referenced-by-count":47,"title":["Dual Oxidase\u20131 Is Required for Airway Epithelial Cell Migration and Bronchiolar Reepithelialization after Injury"],"prefix":"10.1093","volume":"48","author":[{"given":"Stefan H.","family":"Gorissen","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Vermont, Burlington, Vermont"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena","family":"Hristova","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Vermont, Burlington, Vermont"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aida","family":"Habibovic","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Vermont, Burlington, Vermont"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynne M.","family":"Sipsey","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Vermont, Burlington, Vermont"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Page C.","family":"Spiess","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Vermont, Burlington, Vermont"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne M. 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