Abstract
Airway damage and remodelling are important components of lung pathology progression in cystic fibrosis (CF). Although repair mechanisms are engaged to restore the epithelial integrity, these processes are obviously insufficient to maintain lung function in CF airways. Our aims were therefore to study how the basic cystic fibrosis transmembrane conductance regulator (CFTR) defect could impact epithelial wound healing and to determine if CFTR correction could improve it.
Wound-healing experiments, as well as cell migration and proliferation assays, were performed to study the early phases of epithelial repair in human CF and non-CF airway cells. CFTR function was evaluated using CFTR small interferring (si)RNA and inhibitor GlyH101 in non-CF cells, and conversely after CFTR rescue with the CFTR corrector VRT-325 in CF cells.
Wound-healing experiments first showed that airway cells from CF patients repaired slower than non-CF cells. CFTR inhibition or silencing in non-CF primary airway cells significantly inhibited wound closure. GlyH101 also decreased cell migration and proliferation. Interestingly, wild-type CFTR transduction in CF airway cell lines or CFTR correction with VRT-325 in CFBE-ΔF508 and primary CF bronchial monolayers significantly improved wound healing.
Altogether our results demonstrated that functional CFTR plays a critical role in wound repair, and CFTR correction may represent a novel strategy to promote the airway repair processes in CF.
Footnotes
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Support Statement
This study was funded by Cystic Fibrosis Canada (grant to E. Brochiero and studentship to N.T.N Trinh), the Association Vaincre la Mucoviscidose (grant to C. Coraux), the programme d'échange internationaux, FRSQ-INSERM (E. Brochiero and C. Coraux), CRCHUM and Université de Montréal (scholarship to E. Brochiero and studentship to O. Bardou) and the training programme of the Respiratory Health Network and the CIHR (studentship to E. Maillé).
Statement of Interest
None declared.
- Received December 16, 2011.
- Accepted March 6, 2012.
- ©ERS 2012