Pharmacological rescue of mutant CFTR protein improves the viscoelastic properties of CF mucus

Ambra Gianotti, Valeria Capurro, Paolo Scudieri, Luis J V Galietta, Oscar Moran, Olga Zegarra-Moran

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In CF patients, the defective ion transport causes a simultaneous reduction of fluid, Cl- and HCO3 - secretion. We aimed to demonstrate that the resulting altered properties of mucus can be recovered using lumacaftor, a CFTR corrector. Methods: The micro-rheology of non-CF and CF mucus was analysed using Multiple Particle Tracking. Results: The diffusion coefficient of nano-beads imbedded in mucus from CF human bronchial epithelium was lower than in non-CF mucus, and the elastic and viscous moduli were higher. We found that 25% correction of F508del-CFTR mutation with lumacaftor was enough to improve significantly CF mucus properties. Surprisingly, also incubation with amiloride, a compound that reduces fluid absorption but might not change the secretion of HCO3 - towards the airway surface fluid, improved CF mucus properties. Conclusion: CF mucus properties can be recovered by either improving the hydration of the airways or recovering Cl- and HCO3 - secretion across the mutated protein treated with a corrector compound.

Original languageEnglish
JournalJournal of Cystic Fibrosis
DOIs
Publication statusAccepted/In press - Sep 25 2015

Keywords

  • CFTR
  • Ivacaftor
  • Lumacaftor
  • Micro-rheology
  • Mucus
  • Multiple particle tracking

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pediatrics, Perinatology, and Child Health

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