title: Pharmacological rescue of mutant CFTR protein improves the viscoelastic properties of CF mucus.
abstract: 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.
  
  
  
  The micro-rheology of non-CF and CF mucus was analysed using Multiple Particle Tracking.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, via Gaslini, 5, 16148 Genoa, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Gianotti
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, via Gaslini, 5, 16148 Genoa, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Capurro
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, via Gaslini, 5, 16148 Genoa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Scudieri
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, via Gaslini, 5, 16148 Genoa, Italy.
authors.forename: Luis J V
authors.initials: LJ
authors.lastname: Galietta
authors.affiliation: Istituto di Biofisica, Consiglio Nazionale delle Ricerche, via de Marini, 6, 16149 Genoa, Italy.
authors.forename: Oscar
authors.initials: O
authors.lastname: Moran
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, via Gaslini, 5, 16148 Genoa, Italy. Electronic address: ozegarra@unige.it.
authors.forename: Olga
authors.initials: O
authors.lastname: Zegarra-Moran
mesh_terms: D000584:Amiloride / Q000008:administration & dosage / Q000493:pharmacokinetics; D000631:Aminopyridines / Q000008:administration & dosage / Q000493:pharmacokinetics; D052117:Benzodioxoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D018929:Cell Culture Techniques; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D062686:Epithelial Sodium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D044085:Microfluidics / Q000379:methods; D008962:Models, Theoretical; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism
chemical_list: D000631:Aminopyridines; D052117:Benzodioxoles; D062686:Epithelial Sodium Channel Blockers; D050505:Mutant Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride; C569105:lumacaftor
keywords: CFTR; Ivacaftor; Micro-rheology; Mucus; Multiple particle tracking; lumacaftor