Loss of E-cadherin is causal to pathologic changes in chronic lung disease.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
29 10 2022
29 10 2022
Historique:
received:
14
01
2022
accepted:
21
10
2022
pubmed:
31
10
2022
medline:
2
11
2022
entrez:
30
10
2022
Statut:
epublish
Résumé
Epithelial cells line the lung mucosal surface and are the first line of defense against toxic exposures to environmental insults, and their integrity is critical to lung health. An early finding in the lung epithelium of patients with chronic obstructive pulmonary disease (COPD) is the loss of a key component of the adherens junction protein called E-cadherin. The cause of this decrease is not known and could be due to luminal insults or structural changes in the small airways. Irrespective, it is unknown whether the loss of E-cadherin is a marker or a driver of disease. Here we report that loss of E-cadherin is causal to the development of chronic lung disease. Using cell-type-specific promoters, we find that knockout of E-cadherin in alveolar epithelial type II but not type 1 cells in adult mouse models results in airspace enlargement. Furthermore, the knockout of E-cadherin in airway ciliated cells, but not club cells, increase airway hyperreactivity. We demonstrate that strategies to upregulate E-cadherin rescue monolayer integrity and serve as a potential therapeutic target.
Identifiants
pubmed: 36309587
doi: 10.1038/s42003-022-04150-w
pii: 10.1038/s42003-022-04150-w
pmc: PMC9617938
doi:
Substances chimiques
Cadherins
0
Cdh1 protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1149Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : R01-HL124099
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HLR01-HL151107
Informations de copyright
© 2022. The Author(s).
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