Modulation of Wnt signaling is essential for the differentiation of ciliated epithelial cells in human airways

Wnt signaling is essential for the differentiation of airway epithelial cells during development. Here, we examined the role of Wnt signaling during redifferentiation of ciliated airway epithelial cells in vitro at the air liquid interface as a model of airway epithelial repair. Phases of proliferation and differentiation were defined. Markers of squamous metaplasia and epithelial ciliation were followed while enhancing beta-catenin signaling by blocking glycogen synthase kinase 3 beta with SB216763 and shRNA as well as inhibiting canonical WNT signaling with apical application of Dickkopf 1 (Dkk1). Our findings indicate that enhanced beta-catenin signaling decreases the number of ciliated cells and causes squamous changes in the epithelium, whereas treatment with DDk1 leads to an increased number of ciliated cells.