title: Airway epithelial cell migration and wound repair by ATP-mediated activation of dual oxidase 1.
abstract: The airway epithelium is continuously subjected to environmental pollutants, airborne pathogens, and allergens and relies on several intrinsic mechanisms to maintain barrier integrity and to promote epithelial repair processes following injury. Here, we report a critical role for dual oxidase 1 (Duox1), a newly identified NADPH oxidase homolog within the tracheobronchial epithelium, in airway epithelial cell migration and repair following injury. Activation of Duox1 during epithelial injury is mediated by cellular release of ATP, which signals through purinergic receptors expressed on the epithelial cell surface. Purinergic receptor stimulation by extracellular ATP is a critical determinant of epithelial cell migration and repair following injury and is associated with activation of extracellular signal-regulated kinases (ERK1/2) and matrix metalloproteinase-9 (MMP-9). Stimulation of these integral features of epithelial cell migration and repair processes was found to require the activation of Duox1. Our findings demonstrate a novel role for Duox1 in the tracheobronchial epithelium, in addition to its proposed role in antimicrobial host defense, by participating in epithelial repair processes to maintain epithelial integrity and barrier function in the face of environmental stress.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont 05405, USA.
authors.forename: Umadevi V
authors.initials: UV
authors.lastname: Wesley
authors.forename: Peter F
authors.initials: PF
authors.lastname: Bove
authors.forename: Milena
authors.initials: M
authors.lastname: Hristova
authors.forename: Sean
authors.initials: S
authors.lastname: McCarthy
authors.forename: Albert
authors.initials: A
authors.lastname: van der Vliet
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001980:Bronchi; D017931:DNA Primers; D000074623:Dual Oxidases; D005420:Flavoproteins / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020545:Respiratory Mucosa / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea; D014945:Wound Healing
chemical_list: D017931:DNA Primers; D005420:Flavoproteins; D034741:RNA, Small Interfering; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431513:DUOX1 protein, human