Trefoil factor-2 reverses airway remodeling changes in allergic airways disease

Trefoil factor 2/TFF2 is a small peptide with an important role in mucosal repair. TFF2 is up-regulated in asthma suggesting a role in asthma pathogenesis. Given its known biological role in promoting epithelial repair, TFF2 might be expected to have a protective function in limiting the progression of airway remodeling in asthma. The contribution of TFF2 to airway remodeling in asthma was investigated by examining the expression of TFF2 in the airway/lung, and evaluating the effects of recombinant TFF2 treatment on established airway remodeling in a mouse model of chronic allergic airways disease (AAD). Balb/c mice were sensitized and challenged with ovalbumin (OVA) or saline for 9 weeks, while mice with established OVA-induced AAD were treated with TFF2 or vehicle control (intranasally for 14 days). Effects on airway remodeling, airway inflammation and airway hyperresponsiveness were then assessed, while TFF2 expression was determined by immunohistochemistry. TFF2 expression was significantly increased in the airways of mice with AAD as compared to expression levels in controls. TFF2 treatment resulted in reduced epithelial thickening, subepithelial collagen deposition, goblet cell metaplasia, bronchial epithelium apoptosis and airway hyperresponsiveness (all p