Trefoil Factor 2 Regulates Airway Remodeling in Animal Models of Asthma

Abstract

Background. Epithelial denudation and metaplasia are important in the pathogenesis of airway remodeling and asthma. Trefoil factor 2 (TFF2) is a member of a family of peptides involved in protection and healing of the gastrointestinal epithelium but which are also secreted in the airway mucosa. Methods. We investigated the role of TFF2 in airway remodeling by histological and morphometric analysis of lung tissue from TFF2-deficient mice subjected to two relevant animal models of asthma: an ovalbumin model of allergic airways disease and an Aspergillus fumigatus antigen sensitization model. Results. In the ovalbumin model TFF2-deficient mice had increased goblet cell hyperplasia, but not epithelial thickening compared to wild-type (WT) counterparts. In the Aspergillus model TFF2-deficient mice also had increased goblet cell hyperplasia, and epithelial thickness was also increased in the Aspergillus-sensitized mice compared to WT controls. TFF2 deficiency was also associated with increased subepithelial collagen layer thickness. Discussion. The current study demonstrates a role of TFF2 in airway remodeling in mouse models of airway disease. Further studies into the mechanisms of action of TFF2 and its role in asthma are warranted.