eCite Digital Repository

Increased myofibroblasts in the small airways, and relationship to remodelling and functional changes in smokers and COPD patients: potential role of epithelial-mesenchymal transition

Citation

Eapen, MS and LU, W and Hackett, TL and Singhera, GK and Mahmood, MQ and Hardikar, A and Ward, C and Walters, EH and Sohal, SS, Increased myofibroblasts in the small airways, and relationship to remodelling and functional changes in smokers and COPD patients: potential role of epithelial-mesenchymal transition, ERJ Open Research, 7, (2) pp. 1-12. ISSN 2312-0541 (2021) [Refereed Article]


Preview
PDF
Pending copyright assessment - Request a copy
1Mb
  

DOI: doi:10.1183/23120541.00876-2020

Abstract

Introduction: Previous reports have shown epithelial–mesenchymal transition (EMT) as an active process that contributes to small airway fibrotic pathology. Myofibroblasts are highly active pro-fibrotic cells that secrete excessive and altered extracellular matrix (ECM). Here we relate small airway myofibroblast presence with airway remodelling, physiology and EMT activity in smokers and COPD patients.

Methods: Lung resections from nonsmoker controls, normal lung function smokers and COPD current and ex-smokers were stained with anti-human α-smooth muscle actin (SMA), collagen 1 and fibronectin. αSMA+ cells were computed in reticular basement membrane (Rbm), lamina propria and adventitia and presented per mm of Rbm and mm2 of lamina propria. Collagen-1 and fibronectin are presented as a percentage change from normal. All analyses including airway thickness were measured using Image-proplus 7.0.

Results: We found an increase in subepithelial lamina propria (especially) and adventitia thickness in all pathological groups compared to nonsmoker controls. Increases in αSMA+ myofibroblasts were observed in subepithelial Rbm, lamina propria and adventitia in both the smoker and COPD groups compared to nonsmoker controls. Furthermore, the increase in the myofibroblast population in the lamina propria was strongly associated with decrease in lung function, lamina propria thickening, increase in ECM protein deposition, and finally EMT activity in epithelial cells.

Conclusions: This is the first systematic characterisation of small airway myofibroblasts in COPD based on their localisation, with statistically significant correlations between them and other pan-airway structural, lung function and ECM protein changes. Finally, we suggest that EMT may be involved in such changes.

Item Details

Item Type:Refereed Article
Keywords:COPD, epithelium, fibrosis, EMT, Cancer, ICS, IPF, fibroblasts, myofibroblasts, airways
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Cardiology (incl. cardiovascular diseases)
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Eapen, MS (Mr Mathew Eapen)
UTAS Author:LU, W (Dr Monica LU)
UTAS Author:Hardikar, A (Dr Ashutosh Hardikar)
UTAS Author:Walters, EH (Professor Haydn Walters)
UTAS Author:Sohal, SS (Dr Sukhwinder Sohal)
ID Code:145265
Year Published:2021
Deposited By:Health Sciences
Deposited On:2021-07-14
Last Modified:2021-07-20
Downloads:0

Repository Staff Only: item control page