Cadherin Function in Bronchial Epithelial Wound Healing

The bronchial epithelial lining is often impaired in asthma with observed epithelial denudation. Normal epithelium is scaffolded by various adhesion molecules which interact and co-exist in such a fashion that together they support an epithelium that functions to line the airway lumen forming a selectivity permeable barrier, protecting the underlying tissue from harmful noxious agents in the exterior environment.The process of epithelial shedding is not fully understood. Putative restitution stages have been observed where the remaining epithelia undergo flattening, migration, proliferation and differentiation stages to restore an intact epithelial barrier.The detailed examination of bronchial epithelial morphology of non-asthmatic, asthmatic and chronic asthmatic patients in this study revealed characteristic cell phenotypes for each patient grouping. Non-asthmatics in general had an intact uniform epithelium, asthmatics tended to have suprabasal denudation, with 'flattened' basal cells remaining, whereas chronic asthmatics tended to have a predominantly denuded basement membrane with complete cell loss.Using models of epithelial development and repair, this study has demonstrated molecular modifications that are characteristic of these epithelial cell phenotypes. The adherens junction associated cell adhesion molecules E- and P-cadherin were shown to have contrasting expression patterns in epithelial development in vitro. Elevated P-cadherin immunoreactivity was seen at pre-confluence in parallel with a reduction in E-cadherin immunoreactivity. Similar observations in the early stages of repair suggest a disruption of the rigid permanent E-cadherin contacts on epithelial damage, allowing migration and more dynamic adhesion, accompanied by seemingly elevated P-cadherin levels promoting proliferation and differentiation to occur.Epithelial cells transfected with sense and antisense E-cadherin genes demonstrated a co-dependence between the expression of E- and P-cadherin expression. Preliminary work was undertaken to establish cells with altered P-cadherin expression levels. These clones, in conjunction with the epithelial models established in this study will prove essential tools in the investigation of cadherin involvement in epithelial cell adhesion and wound repair.