Epithelial–mesenchymal transition is driven by transcriptional and post transcriptional modulations in COPD: implications for disease progression and new therapeutics

Mathew Suji Eapen,1 Pawan Sharma,1–3 Archana Vijay Gaikwad,1 Wenying Lu,1 Stephen Myers,1 Philip M Hansbro4,5, Sukhwinder Singh Sohal11Respiratory Translational Research Group, Department of Laboratory Medicine, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia; 2Medical Sciences, University of Technology Sydney, Sydney, NSW 2007, Australia; 3Woolcock Emphysema Centre, Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW 2037, Australia; 4Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and the University of Newcastle, Newcastle, NSW 2308, Australia; 5Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, NSW 2007, AustraliaAbstract: COPD is a common and highly destructive disease with huge impacts on people and health services throughout the world. It is mainly caused by cigarette smoking though environmental pollution is also significant. There are no current treatments that affect the overall course of COPD; current drugs focus on symptomatic relief and to some extent reducing exacerbation rates. There is an urgent need for in-depth studies of the fundamental pathogenic mechanisms that underpin COPD. This is vital, given the fact that nearly 40%–60% of the small airway and alveolar damage occurs in COPD well before the first measurable changes in lung function are detected. These individuals are also at a high risk of lung cancer. Current COPD research is mostly centered around late disease and/or innate immune activation within the airway lumen, but the actual damage to the airway wall has early onset. COPD is the end result of complex mechanisms, possibly triggered through initial epithelial activation. To change the disease trajectory, it is crucial to understand the mechanisms in the epithelium that are switched on early in smokers. One such mechanism we believe is the process of epithelial to mesenchymal transition. This article highlights the importance of this profound epithelial cell plasticity in COPD and also its regulation. We consider that understanding early changes in COPD will open new windows for therapy.Keywords: epithelial-to-mesenchymal transition, EMT, cancer, fibrosis, inflammation, HuR, EGFR, MMP, TGFβ