Epithelial-to-mesenchymal transition is an active process in the large airways of patients with asthma-COPD overlap and partially abrogated by inhaled corticosteroid treatment: a bronchoscopy endobronchial biopsy study
IntroductionAsthma and chronic obstructive pulmonary disease (COPD) overlap (ACO) is a term used to describe a patient with coexisting clinical features of asthma and COPD. We have previously reported that epithelial to mesenchymal transition (EMT) is active in the lungs of patients with COPD howeve...
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Frontiers Media S.A.
2025-05-01
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| author | Surajit Dey Wenying Lu Prabuddha S. Pathinayake Maddison Waters Greg Haug Josie Larby Heinrich C. Weber Peter A. B. Wark Peter A. B. Wark Mathew Suji Eapen Sukhwinder Singh Sohal |
| author_facet | Surajit Dey Wenying Lu Prabuddha S. Pathinayake Maddison Waters Greg Haug Josie Larby Heinrich C. Weber Peter A. B. Wark Peter A. B. Wark Mathew Suji Eapen Sukhwinder Singh Sohal |
| author_sort | Surajit Dey |
| collection | DOAJ |
| description | IntroductionAsthma and chronic obstructive pulmonary disease (COPD) overlap (ACO) is a term used to describe a patient with coexisting clinical features of asthma and COPD. We have previously reported that epithelial to mesenchymal transition (EMT) is active in the lungs of patients with COPD however, EMT in ACO remains an unexplored area. We hypothesize that EMT is an active process in ACO.MethodsIn this cross-sectional study, large airway endobronchial biopsy (EBB) tissues from patients with asthma (14), COPD (22), current (CS) and ex-smokers (ES), and ACO (12) were immunohistochemically stained for EMT markers (E and N cadherin, vimentin, S100A4, and Collagen IV) and compared with 12 current smokers with normal lung function (NLFS) and 10 non-smoking healthy control (HC) subjects. In addition, air-liquid interface (ALI) cell cultures were performed and cells from patients with ACO and HC were treated with TGF-β, IL-13 and cigarette smoke extract (CSE). Later cells from ALI cultures were lysed for Immunoblotting. Immunostained tissues were enumerated for percent expression of E and N-Cadherin in the epithelium, vimentin and S100A4 positive cells both in the epithelium and reticular basement membrane (RBM). Additionally, the degree of RBM fragmentation was evaluated, a key tissue structural marker of EMT.ResultsCompared to healthy controls and asthmatics, ACO had the greatest fragmentation of RBM (P < 0.01). ACO also had substantially decreased percentage expression of E-cadherin (P <0.01), increase percentage of N-cadherin expression, and higher vimentin and S100A4 positive basal cells, in comparison to healthy controls. In the RBM of ACO, S100A4 positive cells (P <0.05) and Vimentin-positive cells were markedly higher in comparison to HC. Similar changes were observed with western blots in response to Th-2 cytokine IL-13, CSE and EMT activator TGF-β.ConclusionsThese data are suggestive of active EMT in ACO. Additionally, 50% of the patients with ACO were on 800 mcg/day inhaled corticosteroid (ICS) treatment which may have abrogated some EMT activity; however, it suggests protective effects of ICS as we previously reported in COPD. Studies with larger cohorts are needed to further confirm ICS effects in ACO. |
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| id | doaj-art-00744d2f989744d4bc814c40ebf03f5a |
| institution | OA Journals |
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| publishDate | 2025-05-01 |
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| spelling | doaj-art-00744d2f989744d4bc814c40ebf03f5a2025-08-20T01:55:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15312791531279Epithelial-to-mesenchymal transition is an active process in the large airways of patients with asthma-COPD overlap and partially abrogated by inhaled corticosteroid treatment: a bronchoscopy endobronchial biopsy studySurajit Dey0Wenying Lu1Prabuddha S. Pathinayake2Maddison Waters3Greg Haug4Josie Larby5Heinrich C. Weber6Peter A. B. Wark7Peter A. B. Wark8Mathew Suji Eapen9Sukhwinder Singh Sohal10Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, AustraliaRespiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, AustraliaImmune Health Program, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, AustraliaDepartment of Respiratory Medicine, Launceston General Hospital, Launceston, AustraliaDepartment of Respiratory Medicine, Launceston General Hospital, Launceston, AustraliaDepartment of Respiratory Medicine, Launceston General Hospital, Launceston, AustraliaDepartment of Respiratory Medicine, Tasmanian Health Services (THS), North-West Hospital, Burnie, TAS, AustraliaImmune Health Program, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, AustraliaDepartment of Respiratory Medicine, Monash University, Melbourne, AustraliaRespiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, AustraliaRespiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, AustraliaIntroductionAsthma and chronic obstructive pulmonary disease (COPD) overlap (ACO) is a term used to describe a patient with coexisting clinical features of asthma and COPD. We have previously reported that epithelial to mesenchymal transition (EMT) is active in the lungs of patients with COPD however, EMT in ACO remains an unexplored area. We hypothesize that EMT is an active process in ACO.MethodsIn this cross-sectional study, large airway endobronchial biopsy (EBB) tissues from patients with asthma (14), COPD (22), current (CS) and ex-smokers (ES), and ACO (12) were immunohistochemically stained for EMT markers (E and N cadherin, vimentin, S100A4, and Collagen IV) and compared with 12 current smokers with normal lung function (NLFS) and 10 non-smoking healthy control (HC) subjects. In addition, air-liquid interface (ALI) cell cultures were performed and cells from patients with ACO and HC were treated with TGF-β, IL-13 and cigarette smoke extract (CSE). Later cells from ALI cultures were lysed for Immunoblotting. Immunostained tissues were enumerated for percent expression of E and N-Cadherin in the epithelium, vimentin and S100A4 positive cells both in the epithelium and reticular basement membrane (RBM). Additionally, the degree of RBM fragmentation was evaluated, a key tissue structural marker of EMT.ResultsCompared to healthy controls and asthmatics, ACO had the greatest fragmentation of RBM (P < 0.01). ACO also had substantially decreased percentage expression of E-cadherin (P <0.01), increase percentage of N-cadherin expression, and higher vimentin and S100A4 positive basal cells, in comparison to healthy controls. In the RBM of ACO, S100A4 positive cells (P <0.05) and Vimentin-positive cells were markedly higher in comparison to HC. Similar changes were observed with western blots in response to Th-2 cytokine IL-13, CSE and EMT activator TGF-β.ConclusionsThese data are suggestive of active EMT in ACO. Additionally, 50% of the patients with ACO were on 800 mcg/day inhaled corticosteroid (ICS) treatment which may have abrogated some EMT activity; however, it suggests protective effects of ICS as we previously reported in COPD. Studies with larger cohorts are needed to further confirm ICS effects in ACO.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531279/fullasthma-COPD overlap (ACO)COPD - chronic obstructive pulmonary diseasesmokingfibrosisICS - inhaled corticosteroidshistopathology |
| spellingShingle | Surajit Dey Wenying Lu Prabuddha S. Pathinayake Maddison Waters Greg Haug Josie Larby Heinrich C. Weber Peter A. B. Wark Peter A. B. Wark Mathew Suji Eapen Sukhwinder Singh Sohal Epithelial-to-mesenchymal transition is an active process in the large airways of patients with asthma-COPD overlap and partially abrogated by inhaled corticosteroid treatment: a bronchoscopy endobronchial biopsy study Frontiers in Immunology asthma-COPD overlap (ACO) COPD - chronic obstructive pulmonary disease smoking fibrosis ICS - inhaled corticosteroids histopathology |
| title | Epithelial-to-mesenchymal transition is an active process in the large airways of patients with asthma-COPD overlap and partially abrogated by inhaled corticosteroid treatment: a bronchoscopy endobronchial biopsy study |
| title_full | Epithelial-to-mesenchymal transition is an active process in the large airways of patients with asthma-COPD overlap and partially abrogated by inhaled corticosteroid treatment: a bronchoscopy endobronchial biopsy study |
| title_fullStr | Epithelial-to-mesenchymal transition is an active process in the large airways of patients with asthma-COPD overlap and partially abrogated by inhaled corticosteroid treatment: a bronchoscopy endobronchial biopsy study |
| title_full_unstemmed | Epithelial-to-mesenchymal transition is an active process in the large airways of patients with asthma-COPD overlap and partially abrogated by inhaled corticosteroid treatment: a bronchoscopy endobronchial biopsy study |
| title_short | Epithelial-to-mesenchymal transition is an active process in the large airways of patients with asthma-COPD overlap and partially abrogated by inhaled corticosteroid treatment: a bronchoscopy endobronchial biopsy study |
| title_sort | epithelial to mesenchymal transition is an active process in the large airways of patients with asthma copd overlap and partially abrogated by inhaled corticosteroid treatment a bronchoscopy endobronchial biopsy study |
| topic | asthma-COPD overlap (ACO) COPD - chronic obstructive pulmonary disease smoking fibrosis ICS - inhaled corticosteroids histopathology |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531279/full |
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