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

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

Research output: Contribution to journalArticle

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
Pages (from-to)295-301
Number of pages7
JournalJournal of Cystic Fibrosis
Volume15
Issue number3
DOIs
Publication statusPublished - May 2016

Keywords

  • Journal Article

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    Gianotti, A., Capurro, V., Scudieri, P., Galietta, L. J. V., Moran, O., & Zegarra Moran, O. (2016). Pharmacological rescue of mutant CFTR protein improves the viscoelastic properties of CF mucus. Journal of Cystic Fibrosis, 15(3), 295-301. https://doi.org/10.1016/j.jcf.2015.11.003