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Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond
The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel for transport of chloride and bicarbonate anions. Functional roles of CFTR have been identified in a broad range of cell types including epithelial, endothelial, immune and structural cells. While CFTR has been i...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
European Respiratory Society
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066568/ https://www.ncbi.nlm.nih.gov/pubmed/37003609 http://dx.doi.org/10.1183/13993003.01307-2022 |
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author | Mall, Marcus A. Criner, Gerard J. Miravitlles, Marc Rowe, Steven M. Vogelmeier, Claus F. Rowlands, David J. Schoenberger, Matthias Altman, Pablo |
author_facet | Mall, Marcus A. Criner, Gerard J. Miravitlles, Marc Rowe, Steven M. Vogelmeier, Claus F. Rowlands, David J. Schoenberger, Matthias Altman, Pablo |
author_sort | Mall, Marcus A. |
collection | PubMed |
description | The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel for transport of chloride and bicarbonate anions. Functional roles of CFTR have been identified in a broad range of cell types including epithelial, endothelial, immune and structural cells. While CFTR has been investigated largely in the context of inborn dysfunction in cystic fibrosis, recent evidence shows that CFTR is also affected by acquired dysfunction in COPD. In patients with COPD and smokers, CFTR impairment has been demonstrated in the upper and lower airways, sweat glands and intestines, suggesting both pulmonary and systemic defects. Cigarette smoke, a key factor in COPD development, is the major cause of acquired CFTR dysfunction. Inflammation, bacterial byproducts and reactive oxygen species can further impair CFTR expression and function. CFTR dysfunction could contribute directly to disease manifestation and progression of COPD including disturbed airway surface liquid homeostasis, airway mucus obstruction, pathogen colonisation and inflammation. Mucus plugging and neutrophilic inflammation contribute to tissue destruction, development of dysfunction at the level of the small airways and COPD progression. Acquired CFTR dysfunction in extrapulmonary organs could add to common comorbidities and the disease burden. This review explores how CFTR dysfunction may be acquired and its potential effects on patients with COPD, particularly those with chronic bronchitis. The development of CFTR potentiators and the probable benefits of CFTR potentiation to improve tissue homeostasis, reduce inflammation, improve host defence and potentially reduce remodelling in the lungs will be discussed. |
format | Online Article Text |
id | pubmed-10066568 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | European Respiratory Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-100665682023-04-02 Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond Mall, Marcus A. Criner, Gerard J. Miravitlles, Marc Rowe, Steven M. Vogelmeier, Claus F. Rowlands, David J. Schoenberger, Matthias Altman, Pablo Eur Respir J Reviews The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel for transport of chloride and bicarbonate anions. Functional roles of CFTR have been identified in a broad range of cell types including epithelial, endothelial, immune and structural cells. While CFTR has been investigated largely in the context of inborn dysfunction in cystic fibrosis, recent evidence shows that CFTR is also affected by acquired dysfunction in COPD. In patients with COPD and smokers, CFTR impairment has been demonstrated in the upper and lower airways, sweat glands and intestines, suggesting both pulmonary and systemic defects. Cigarette smoke, a key factor in COPD development, is the major cause of acquired CFTR dysfunction. Inflammation, bacterial byproducts and reactive oxygen species can further impair CFTR expression and function. CFTR dysfunction could contribute directly to disease manifestation and progression of COPD including disturbed airway surface liquid homeostasis, airway mucus obstruction, pathogen colonisation and inflammation. Mucus plugging and neutrophilic inflammation contribute to tissue destruction, development of dysfunction at the level of the small airways and COPD progression. Acquired CFTR dysfunction in extrapulmonary organs could add to common comorbidities and the disease burden. This review explores how CFTR dysfunction may be acquired and its potential effects on patients with COPD, particularly those with chronic bronchitis. The development of CFTR potentiators and the probable benefits of CFTR potentiation to improve tissue homeostasis, reduce inflammation, improve host defence and potentially reduce remodelling in the lungs will be discussed. European Respiratory Society 2023-04-03 /pmc/articles/PMC10066568/ /pubmed/37003609 http://dx.doi.org/10.1183/13993003.01307-2022 Text en Copyright ©The authors 2023. https://creativecommons.org/licenses/by-nc/4.0/This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org (mailto:permissions@ersnet.org) |
spellingShingle | Reviews Mall, Marcus A. Criner, Gerard J. Miravitlles, Marc Rowe, Steven M. Vogelmeier, Claus F. Rowlands, David J. Schoenberger, Matthias Altman, Pablo Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond |
title | Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond |
title_full | Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond |
title_fullStr | Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond |
title_full_unstemmed | Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond |
title_short | Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond |
title_sort | cystic fibrosis transmembrane conductance regulator in copd: a role in respiratory epithelium and beyond |
topic | Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066568/ https://www.ncbi.nlm.nih.gov/pubmed/37003609 http://dx.doi.org/10.1183/13993003.01307-2022 |
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