Anoctamin 1 dysregulation alters bronchial epithelial repair in cystic fibrosis.
Biochim Biophys Acta
; 1832(12): 2340-51, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-24080196
ABSTRACT
Cystic fibrosis (CF) airway epithelium is constantly subjected to injury events due to chronic infection and inflammation. Moreover, abnormalities in CF airway epithelium repair have been described and contribute to the lung function decline seen in CF patients. In the last past years, it has been proposed that anoctamin 1 (ANO1), a Ca(2+)-activated Cl(-) channel, might offset the CFTR deficiency but this protein has not been characterized in CF airways. Interestingly, recent evidence indicates a role for ANO1 in cell proliferation and tumor growth. Our aims were to study non-CF and CF bronchial epithelial repair and to determine whether ANO1 is involved in airway epithelial repair. Here, we showed, with human bronchial epithelial cell lines and primary cells, that both cell proliferation and migration during epithelial repair are delayed in CF compared to non-CF cells. We then demonstrated that ANO1 Cl(-) channel activity was significantly decreased in CF versus non-CF cells. To explain this decreased Cl(-) channel activity in CF context, we compared ANO1 expression in non-CF vs. CF bronchial epithelial cell lines and primary cells, in lung explants from wild-type vs. F508del mice and non-CF vs. CF patients. In all these models, ANO1 expression was markedly lower in CF compared to non-CF. Finally, we established that ANO1 inhibition or overexpression was associated respectively with decreases and increases in cell proliferation and migration. In summary, our study demonstrates involvement of ANO1 decreased activity and expression in abnormal CF airway epithelial repair and suggests that ANO1 correction may improve this process.
Palavras-chave
ANO1; Airway; Anoctamin 1; Bronchial epithelial repair; CF; CI; CaCC; Cell proliferation; Cystic fibrosis; F508del; RTCA; TMEM16a; WGA; anoctamin 1; calcium-activated chloride channel; cystic fibrosis; normalized cell index; phenylalanine 508 deletion; real time cell analysis; transmembrane 16a protein; wheat germ agglutinin
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Brônquios
/
Canais de Cloreto
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Regulador de Condutância Transmembrana em Fibrose Cística
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Mucosa Respiratória
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Fibrose Cística
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Células Epiteliais
/
Pulmão
/
Proteínas de Neoplasias
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Animals
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Humans
/
Middle aged
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
França