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Improvement of defective cystic fibrosis airway epithelial wound repair after CFTR rescue.
MedLine Citation:
PMID:  22496330     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 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 siRNA 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, wt-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.
Authors:
Nguyen Thu Ngan Trinh; Olivier Bardou; Anik Privé; Emilie Maillé; Damien Adam; Sarah Lingée; Pasquale Ferraro; Martin-Yvon Desrosiers; Christelle Coraux; Emmanuelle Brochiero
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-10
Journal Detail:
Title:  The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology     Volume:  -     ISSN:  1399-3003     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Université de Montréal, Montréal, Québec, Canada.
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