The role of mRNA stability in airway remodelling

As a consequence of long-term exposure to inflammatory mediators, the airways of asthmatics become remodelled. Airway fibrosis becomes apparent, with thickening of the lamina recticularis and increased interstitial matrix deposition being typical features of an asthmatic airway. Mucus hypersecretion occurs, airway smooth muscle mass is increased and neovascularization is evident in the subepithelial mucosa. As development of a remodelled airway is correlated with deterioration of lung function in asthmatics, there is an urgent need for therapies that reduce airway inflammation and reverse structural changes in a remodelled airway. However, in order to design efficacious anti-remodelling agents we first need a greater understanding of the molecular mechanism/s underlying the development of airway remodelling. To date, however, most studies have primarily focused on the transcriptional regulation of genes that promote airway remodelling. Post-transcriptional mechanisms, such as control of mRNA stability, remain largely unexplored. Levels of cellular mRNA transcripts are regulated by controlling the rate at which the mRNA decays, thus investigation into the mechanisms underlying mRNA stability in asthma are of critical importance. Therefore, this review will present an overview of the control of mRNA stability and examine how mRNA stability may play a role in the development of airway remodelling in asthma.