Apical dehydration impairs the cystic fibrosis airway epithelium barrier via a ß1-integrin/YAP1 pathway.
Life Sci Alliance
; 7(4)2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38336456
ABSTRACT
Defective hydration of airway surface mucosa is associated with lung infection in cystic fibrosis (CF), partly caused by disruption of the epithelial barrier integrity. Although rehydration of the CF airway surface liquid (ASL) alleviates epithelium vulnerability to infection by junctional protein expression, the mechanisms linking ASL to barrier integrity are unknown. We show here the strong degradation of YAP1 and TAZ proteins in well-polarized CF human airway epithelial cells (HAECs), a process that was prevented by ASL rehydration. Conditional silencing of YAP1 in rehydrated CF HAECs indicated that YAP1 expression was necessary for the maintenance of junctional complexes. A higher plasma membrane tension in CF HAECs reduced endocytosis, concurrent with the maintenance of active ß1-integrin ectopically located at the apical membrane. Pharmacological inhibition of ß1-integrin accumulation restored YAP1 expression in CF HAECs. These results indicate that dehydration of the CF ASL affects epithelial plasma membrane tension, resulting in ectopic activation of a ß1-integrin/YAP1 signaling pathway associated with degradation of junctional proteins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Fibrose Cística
/
Epitélio
Limite:
Humans
Idioma:
En
Revista:
Life Sci Alliance
/
Life sci. alliance
/
Life science alliance
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suíça
País de publicação:
Estados Unidos