We have shown that cell compression alters airway function by increasing collagen deposition, cell turnover, mucus production and impairing anti-viral responses. Conversely, little is known about the impact of shear stress on airway physiology, the only published work is in cystic fibrosis, where shear stress alters airway surface liquid homeostasis, leading to airway obstruction.
We have early preliminary data showing that increased shear stress on cells from asthmatics causes increased apical ATP release compared non-asthmatics. We hypothesise that increased shear stress caused by bronchoconstriction in asthma disrupts epithelial cell function, accelerating disease progression.
This proposal aims to identify pathways upregulated by shear stress and their role in asthma pathogenesis. If shear stress is important in asthma, this may provide an additional point for clinical intervention.