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Improvement of defective Cystic fibrosis airway epithelial repair after CFTR rescue
Author(s) -
Trinh Nguyen Thu Ngan,
Adam Damien,
Bardou Olivier,
Anik Privé,
Maillé Émilie,
Lingée Sarah,
Ferraro Pasquale,
Desrosiers Martin,
Coraux Christelle,
Brochiero Emmanuelle
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.56.9
Subject(s) - cystic fibrosis , wound healing , airway , regeneration (biology) , desquamation , fibrosis , epithelium , pathology , medicine , microbiology and biotechnology , cancer research , biology , immunology , surgery
Airway damage and remodelling is an important component of the progression of lung cystic fibrosis (CF) pathology. Our histological analyses of bronchial tissues from CF patients revealed several ultrastructural anomalies, including epithelial desquamation and tissue remodelling. Although some areas were in the process of epithelial regeneration, the repair mechanisms seemed obviously insufficient in maintaining epithelial integrity in CF airways. Our aim was thus to study the CFTR function in airway repair processes. Wound‐healing assays were performed to study the early phase of epithelial repair, in particular cell migration, in human CF and non‐CF airway cells. Our experiments showed that airway cells from CF patients repaired slower than non‐CF cells. In addition, CFTR inhibition or silencing in non‐CF primary airway cell monolayers partially inhibited wound‐closure. Interestingly, wt‐CFTR transduction in CF airway cell lines or CFTR correction with VRT‐325 in CFBE‐ΔF508 cells and primary CF bronchial monolayers significantly improved wound‐healing. Altogether our results demonstrated that functional CFTR play a critical role in wound‐repair, and CFTR correction may represent a novel strategy to promote the airway repair processes in CF. Project funded by CFC (Cystic Fibrosis Canada).