mahmood-increasedmyofibroblasts-2021.pdf (1.03 MB)
Increased myofibroblasts in the small airways, and relationship to remodelling and functional changes in smokers and COPD patients: potential role of epithelial–mesenchymal transition
journal contribution
posted on 2021-04-01, 00:00 authored by Mathew Suji Eapen, Wenying Lu, Tillie L Hackett, Gurpreet Kaur Singhera, Malik Quasir MahmoodMalik Quasir Mahmood, Ashutosh Hardikar, Chris Ward, Eugene Haydn Walters, Sukhwinder Singh SohalIntroduction 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-pro-plus 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.
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Journal
ERJ open researchVolume
7Issue
2Article number
00876-2020Pagination
1 - 12Publisher
European Respiratory Society (ERS)Location
Sheffield, Eng.Publisher DOI
ISSN
2312-0541eISSN
2312-0541Language
engPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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