Publication
Title
Loss of ciliated cells and altered airway epithelial integrity in cystic fibrosis
Author
Abstract
Background In cystic fibrosis, the respiratory epithelium is the target tissue of both the genetic abnormality of the disease and of external aggressions, notably by pathogens (Pseudomonas aeruginosa). A detailed characterisation of the cystic fibrosis bronchial epithelium is however lacking, as most previous studies focused on the nasal epithelium or on cell lines. This study aimed to characterise the abnormal phenotype and epithelial-to-mesenchymal transition in cystic fibrosis bronchial epithelium and to evaluate in cell cultures whether abnormalities persist ex vivo. Methods Explant lung tissues (n = 44) were assessed for bronchial epithelial cell phenotyping by immunostaining. Human bronchial epithelial cells were derived from basal cells isolated from cystic fibrosis patients or control donors and cultured in air-liquid interface for 2, 4 or 6 weeks. Results Enhanced mucin 5AC and decreased β-tubulin expression were observed in cystic fibrosis airways reflecting a decreased ciliated/goblet cell ratio, associated with increased number of vimentin-positive cells, indicating epithelial-to-mesenchymal transition process. These features were recapitulated in vitro, in cystic fibrosis-derived reconstituted epithelium. However, they were not induced by CFTR inhibition or Pseudomonas infection, and most abnormalities tended to disappear in long-term culture (6 weeks) except for increased fibronectin release, an epithelial-to-mesenchymal transition marker. Conclusions This study provides new insights into airway epithelial changes in cystic fibrosis, which are imprinted through an acquired mechanism that we could not relate to CFTR function.
Language
English
Source (journal)
Journal of cystic fibrosis. - Viborg
Publication
Viborg : 2021
ISSN
1569-1993
DOI
10.1016/J.JCF.2021.09.019
Volume/pages
20 :6 (2021) , p. e129-e139
ISI
000726994200009
Pubmed ID
34657818
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Research group
Publication type
Subject
External links
Web of Science
Record
Identifier
Creation 25.01.2024
Last edited 26.01.2024
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