Progressive loss of dual oxidase 1 (DUOX1) contributes to impaired airway epithelial wound responses in the aging lung

摘要: Age-related chronic diseases, including respiratory diseases such as COPD, are associated with organ function decline, impaired regenerative capacity, and immuno-senescence. Our recent studies indicate that reparative processes in the lung mediated by innate epithelial injury responses production of reactive oxygen species (ROS) NADPH oxidase dual 1 (DUOX1), which were found to be oxidation activation tyrosine kinases, epidermal growth factor receptor (EGFR) non-receptor kinase Src, also secretion alarmins IL-33, promote regeneration activating type 2 immune responses. Contrasting common belief aging is increased ROS production, we observed DUOX1 expression mouse lungs markedly decreases age. Moreover, noticed DUOX1-deficient mice display accelerated age-related decline features emphysema, shown airspace enlargement compliance. We hypothesized loss may contribute other aging, but aged-related changes parenchymal collagen deposition, molecular indices senescence, or tissue levels pro-inflammatory cytokines, all largely unaltered mice. However, aged attenuated airway inhaled allergens, illustrated diminished IL-33 related cytokines. Similar findings vitro using cultured tracheal cells (MTEC), MTECs from older showed dramatically reduced injury, was Src EGFR. Consistent a potential suppression epigenetic mechanisms promoter hypermethylation, allergen-induced could rescued treatment DNA methyltransferase inhibitor AzdC. Overall, these results underline importance host defense contributes impairment capacity air-space enlargement.