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Altered generation of ciliated cells in chronic obstructive pulmonary disease

In COPD, epithelial changes are prominent features in the airways, such as goblet cell hyperplasia and squamous metaplasia. In contrast, it remains unclear whether ciliated cells are reduced and which pathways dysregulate epithelial differentiation. We hypothesized that bronchial epithelial cell lin...

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Autores principales: Gohy, Sophie, Carlier, François M., Fregimilicka, Chantal, Detry, Bruno, Lecocq, Marylène, Ladjemi, Maha Zohra, Verleden, Stijn, Hoton, Delphine, Weynand, Birgit, Bouzin, Caroline, Pilette, Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884487/
https://www.ncbi.nlm.nih.gov/pubmed/31784664
http://dx.doi.org/10.1038/s41598-019-54292-x
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author Gohy, Sophie
Carlier, François M.
Fregimilicka, Chantal
Detry, Bruno
Lecocq, Marylène
Ladjemi, Maha Zohra
Verleden, Stijn
Hoton, Delphine
Weynand, Birgit
Bouzin, Caroline
Pilette, Charles
author_facet Gohy, Sophie
Carlier, François M.
Fregimilicka, Chantal
Detry, Bruno
Lecocq, Marylène
Ladjemi, Maha Zohra
Verleden, Stijn
Hoton, Delphine
Weynand, Birgit
Bouzin, Caroline
Pilette, Charles
author_sort Gohy, Sophie
collection PubMed
description In COPD, epithelial changes are prominent features in the airways, such as goblet cell hyperplasia and squamous metaplasia. In contrast, it remains unclear whether ciliated cells are reduced and which pathways dysregulate epithelial differentiation. We hypothesized that bronchial epithelial cell lineage specification is dysregulated in COPD because of an aberrant reprogramming through transforming growth factor (TGF)-β1. Surgical lung tissue from 81 COPD and 61 control (smokers and non-smokers) patients was assessed for bronchial epithelial cell phenotyping by immunohistochemistry, both in situ and in vitro in reconstituted air-liquid interface (ALI) cultures. The role of TGF-β1 was studied in vitro. COPD epithelium in large airways, when compared to controls, showed decreased β-tubulin IV + ciliated cells (4.4%, 2.5–8.8% versus 8.5%, 6.3–11.8% of surface staining, median and IQR, p = 0.0009) and increased MUC5AC + goblet cells (34.8%, 24.4–41.9% versus 10.3%, 5.1–17.6%, p < 0.0001). Both features were recapitulated in the ALI-cultured epithelium from COPD patients. Exogenous TGF-β1 reduced mucociliary differentiation while neutralizing TGF-β1 during ALI increased both specialized cell types. The COPD airway epithelium displays altered differentiation for ciliated cells, which recapitulates in vitro, at least in part through TGF-β1.
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spelling pubmed-68844872019-12-06 Altered generation of ciliated cells in chronic obstructive pulmonary disease Gohy, Sophie Carlier, François M. Fregimilicka, Chantal Detry, Bruno Lecocq, Marylène Ladjemi, Maha Zohra Verleden, Stijn Hoton, Delphine Weynand, Birgit Bouzin, Caroline Pilette, Charles Sci Rep Article In COPD, epithelial changes are prominent features in the airways, such as goblet cell hyperplasia and squamous metaplasia. In contrast, it remains unclear whether ciliated cells are reduced and which pathways dysregulate epithelial differentiation. We hypothesized that bronchial epithelial cell lineage specification is dysregulated in COPD because of an aberrant reprogramming through transforming growth factor (TGF)-β1. Surgical lung tissue from 81 COPD and 61 control (smokers and non-smokers) patients was assessed for bronchial epithelial cell phenotyping by immunohistochemistry, both in situ and in vitro in reconstituted air-liquid interface (ALI) cultures. The role of TGF-β1 was studied in vitro. COPD epithelium in large airways, when compared to controls, showed decreased β-tubulin IV + ciliated cells (4.4%, 2.5–8.8% versus 8.5%, 6.3–11.8% of surface staining, median and IQR, p = 0.0009) and increased MUC5AC + goblet cells (34.8%, 24.4–41.9% versus 10.3%, 5.1–17.6%, p < 0.0001). Both features were recapitulated in the ALI-cultured epithelium from COPD patients. Exogenous TGF-β1 reduced mucociliary differentiation while neutralizing TGF-β1 during ALI increased both specialized cell types. The COPD airway epithelium displays altered differentiation for ciliated cells, which recapitulates in vitro, at least in part through TGF-β1. Nature Publishing Group UK 2019-11-29 /pmc/articles/PMC6884487/ /pubmed/31784664 http://dx.doi.org/10.1038/s41598-019-54292-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Gohy, Sophie
Carlier, François M.
Fregimilicka, Chantal
Detry, Bruno
Lecocq, Marylène
Ladjemi, Maha Zohra
Verleden, Stijn
Hoton, Delphine
Weynand, Birgit
Bouzin, Caroline
Pilette, Charles
Altered generation of ciliated cells in chronic obstructive pulmonary disease
title Altered generation of ciliated cells in chronic obstructive pulmonary disease
title_full Altered generation of ciliated cells in chronic obstructive pulmonary disease
title_fullStr Altered generation of ciliated cells in chronic obstructive pulmonary disease
title_full_unstemmed Altered generation of ciliated cells in chronic obstructive pulmonary disease
title_short Altered generation of ciliated cells in chronic obstructive pulmonary disease
title_sort altered generation of ciliated cells in chronic obstructive pulmonary disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884487/
https://www.ncbi.nlm.nih.gov/pubmed/31784664
http://dx.doi.org/10.1038/s41598-019-54292-x
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