Late Breaking Abstract - Role of ß-catenin and Notch signalling in increased airway mucous cell differentiation in asthma

Increased activation of β-catenin and Notch signalling pathways in vivo leads to increased airway mucous cell differentiation, a common feature of asthma. Both these pathways play key roles in the normal development and maintenance of airway epithelium but appear to be dysregulated in asthma. While increased β-catenin activates Notch signalling in intestinal epithelium, it is not clear whether this occurs in asthmatic airway epithelium. We hypothesise that in the asthmatic airway, elevated β-catenin signalling activates Notch resulting in increased mucous cell differentiation. To test this, we modelled asthmatic (n=10) and healthy airway (n=10) epithelium using air-liquid interface (ALI) cultures and compared the activities of β-catenin, Notch, and the expression of their respective targets. Immunohistochemistry (IHC) and qPCR analyses were performed at different stages of epithelial development; 0, 11, 20, and 28 days. IHC staining revealed varying levels of active β-catenin and Notch1 in primary bronchial epithelial cells (PBECs) from healthy and asthma groups during development. There was no significant difference in mRNA expression of β-catenin and Notch targets; Cyclin D1 and Hes1 between healthy and asthma groups during development. Additionally, differentiation markers FOXJ1, FOXA2 and MUC5AC were not found to be significantly different in healthy and asthma groups. Therefore, our data shows that there was no significant difference in β-catenin and Notch signalling between PBECs from asthma and healthy donors. We are currently activating/inhibiting β-catenin and/or Notch pathways in healthy PBECs to get a better understanding of the mechanism of mucous cell differentiation.