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.
Highlights
Both dual oxidase (Duox) isozymes contain two EF-hand Ca2ϩ-binding domains and are activated by Ca2ϩ-mobilizing stimuli [11, 12]
ATP-mediated autocrine or paracrine signaling is known to regulate diverse processes involved in host defense, including anion transport, ciliary function, and mucin expression (16 –19), and some of these events have recently been associated with dual oxidase 1 (Duox1) activation [5, 6, 10]
ATP Release Promotes Epithelial Cell Migration by Purinergic Signaling—To investigate the signaling mechanisms in epithelial cell migration and repair, we used an in vitro model of epithelial injury, which involves generating a linear scratch of Ϯ0.2 mm width in confluent monolayers of either NHBE cells or immortalized human tracheobronchial epithelial cells (HBE1)
Summary
Both Duox isozymes contain two EF-hand Ca2ϩ-binding domains and are activated by Ca2ϩ-mobilizing stimuli [11, 12]. We explored whether ATP release mediates airway epithelial cell migration and wound repair following injury and investigated the potential involvement of Duox1 activation in this process.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
