Review Article | Published:

Heparin-binding epidermal growth factor (HB-EGF) drives EMT in patients with COPD: implications for disease pathogenesis and novel therapies

Laboratory Investigationvolume 99pages150157 (2019) | Download Citation

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive and devastating chronic lung condition that has a significant global burden, both medically and financially. Currently there are no medications that can alter the course of disease. At best, the drugs in clinical practice provide symptomatic relief to suffering patients by alleviating acute exacerbations. Most of current clinical research activities are in late severe disease with lesser attention given to early disease manifestations. There is as yet, a lack of understanding of the underlying mechanisms of disease progression and the molecular switches that are involved in their manifestation. Small airway fibrosis and obliteration are known to cause fixed airflow obstruction in COPD, and the consequential damage to the lung has an early onset. So far, there is little evidence of the mechanisms that underlie this aspect of pathology. However, emerging research confirms that airway epithelial reprogramming or epithelial to mesenchymal transition (EMT) is a key mechanism that drives fibrotic remodelling changes in smokers and patients with COPD. A recent study by Lai et al. further highlights the importance of EMT in smoking-related COPD pathology. The authors identify HB-EGF, an EGFR ligand, as a key driver of EMT and a potential new therapeutic target for the amelioration of EMT and airway remodelling. There are also wider implications in lung cancer prophylaxis, which is another major comorbidity associated with COPD. We consider that improved molecular understanding of the intricate pathways associated with epithelial cell plasticity in smokers and patients with COPD will have major therapeutic implications.

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Acknowledgements

SSS is supported by Clifford Craig Foundation Launceston and Thoracic Society of Australia and New Zealand (TSANZ) and Boehringer Ingelheim COPD Research Award, PS is supported by Rebecca L. Cooper Medical Research Foundation, Australia and Chancellors Fellowship Programme, University of Technology Sydney (UTS). PMH is supported by an NHMRC Principal Research Fellowship and a Brawn Fellowship, Faculty of Health, University of Newcastle.

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Affiliations

  1. Respiratory Translational Research Group, Department of Laboratory Medicine, College of Health and Medicine, University of Tasmania, Launceston, TAS, 7248, Australia

    • Mathew Suji Eapen
    • , Isobel E. Thompson
    • , Wenying Lu
    • , Stephen Myers
    •  & Sukhwinder Singh Sohal
  2. Medical Sciences, University of Technology Sydney, Sydney, NSW, 2007, Australia

    • Pawan Sharma
  3. Woolcock Emphysema Centre, Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, 2037, Australia

    • Pawan Sharma
  4. Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, NSW, Australia

    • Philip M. Hansbro
  5. Centenary Institute and University of Technology Sydney, Sydney, NSW, 2007, Australia

    • Philip M. Hansbro

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The authors declare that they have no conflict of interest.

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Correspondence to Sukhwinder Singh Sohal.

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https://doi.org/10.1038/s41374-018-0146-0