Airway remodeling disease: primary human structural cells and phenotypic and pathway assays to identify targets with potential to prevent or reverse remodeling

Elizabeth M Rosethorne,1–3 Steven J Charlton1–3 1School of Life Sciences, Queen’s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK; 2Centre of Membrane and Protein and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands, UK; 3Excellerate Bioscience Ltd, MediCity, Nottingham NG7 2UH, UK Abstract: Airway remodeling is a characteristic of many chronic respiratory diseases and occurs when there are significant changes to the architecture of the small and large airways leading to progressive loss of lung function. Some common features include airway smooth muscle and goblet cell hyperplasia, basement membrane thickening and subepithelial fibrosis. To explore the mechanisms driving airway remodeling and identify novel targets to treat this aspect of respiratory disease, appropriate models must be used that will accurately predict the pathology of disease. Phenotypic assays can be used in primary human lung cells to measure changes in cell behavior that are associated with particular disease pathology. This is becoming increasingly popular when targeting chronic pathologies such as airway remodeling, where phenotypic assays are likely to model disease in vitro more accurately than traditional second messenger assays. Here we review the use of primary human lung structural cells in a range of disease-relevant chronic phenotypic assays, and how they may be used in target identification/validation and drug discovery. Keywords: respiratory, fibroblast, smooth muscle, differentiation, hyperplasia&nbsp