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

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Eapen, MS ORCID: 0000-0003-0570-7059, LU, W ORCID: 0000-0003-1550-2276, Hackett, TL, Singhera, GK, Mahmood, MQ, Hardikar, A, Ward, C, Walters, EH ORCID: 0000-0002-0993-4374 and Sohal, SS ORCID: 0000-0001-9627-6498 2021 , '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, vol. 7, no. 2 , pp. 1-12 , doi: 10.1183/23120541.00876-2020.

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Abstract

Introduction: Previous reports have shown epithelial–mesenchymal transition (EMT) as an active processthat contributes to small airway fibrotic pathology. Myofibroblasts are highly active pro-fibrotic cells thatsecrete excessive and altered extracellular matrix (ECM). Here we relate small airway myofibroblastpresence with airway remodelling, physiology and EMT activity in smokers and COPD patients.Methods: Lung resections from nonsmoker controls, normal lung function smokers and COPD currentand 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 andpresented per mm of Rbm and mm2 of lamina propria. Collagen-1 and fibronectin are presented as apercentage 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 allpathological groups compared to nonsmoker controls. Increases in αSMA+ myofibroblasts were observedin subepithelial Rbm, lamina propria and adventitia in both the smoker and COPD groups compared tononsmoker controls. Furthermore, the increase in the myofibroblast population in the lamina propria wasstrongly associated with decrease in lung function, lamina propria thickening, increase in ECM proteindeposition, and finally EMT activity in epithelial cells.Conclusions: This is the first systematic characterisation of small airway myofibroblasts in COPD based ontheir 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 Type: Article
Authors/Creators: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
Keywords: COPD, epithelium, fibrosis, EMT, Cancer, ICS, IPF, fibroblasts, myofibroblasts, airways
Journal or Publication Title: ERJ Open Research
Publisher: European Respiratory Society
ISSN: 2312-0541
DOI / ID Number: 10.1183/23120541.00876-2020
Copyright Information:

Copyright © The authors 2021. This version is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0. International (CC BY-NC 4.0) license (https://creativecommons.org/licenses/by-nc/4.0/)

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