Novel gene candidates for Airway Remodelling in Asthma

Abstract

Asthma is a complex chronic inflammatory disease regulated by the interplay of a large number of underlying mechanisms which contribute to the overall pathology. A number of structural changes occur in the asthmatic airways including increase in the mass of airway smooth muscle, angiogenesis and mucus hypersecretion which is collectively known as airway remodelling. The experiments in this thesis have for the first time directly compared airway smooth muscle (ASMC) gene expression profiles from asthmatic and healthy patients with the aim to identify genes contributing to asthma and airway remodelling. The latrophilin family members and CCL20 were identified as being up-regulated in asthmatic ASMC compared to healthy controls under basal and inflammatory conditions, respectively. CCL20 was up regulated by moderate asthmatic ASMC and sputum concentrations of CCL20 were found to inversely correlate with lung function. LPHN1 and 3 were found to be up-regulated in ASMC and were found to play a key role in the hyper contractility and increased abundance of ASM mass in the asthmatic airway. The findings present in this thesis have enhanced our understanding of the genes involved in the remodelling process in asthma and identified potential gene targets for future therapies.