RT info:eu-repo/semantics/article
T1 Small Molecule Anion Carriers Correct Abnormal Airway Surface Liquid Properties in Cystic Fibrosis Airway Epithelia
A1 Gianotti, Ambra
A1 Capurro, Valeria
A1 Delpiano, Livia
A1 Mielczarek, Marcin
A1 García Valverde, María
A1 Carreira Barral, Israel
A1 Ludovico, Alessandra
A1 Fiore, Michele
A1 Baroni, Debora
A1 Moran, Óscar
A1 Quesada Pato, Roberto
A1 Caci, Emanuela
K1 Cystic fibrosis
K1 Anionophore
K1 Bronchial epithelial cells culture
K1 Ion transport
K1 Periciliar mucus properties
K1 Medicina
K1 Medicine
K1 Salud
K1 Health
K1 Química orgánica
K1 Chemistry, Organic
AB Cystic fibrosis (CF) is a genetic disease characterized by the lack of cystic fibrosis transmembrane conductance regulator (CFTR) protein expressed in epithelial cells. The resulting defective chloride and bicarbonate secretion and imbalance of the transepithelial homeostasis lead to abnormal airway surface liquid (ASL) composition and properties. The reduced ASL volume impairs ciliary beating with the consequent accumulation of sticky mucus. This situation prevents the normal mucociliary clearance, favouring the survival and proliferation of bacteria and contributing to the genesis of CF lung disease. Here, we have explored the potential of small molecules capable of facilitating the transmembrane transport of chloride and bicarbonate in order to replace the defective transport activity elicited by CFTR in CF airway epithelia. Primary human bronchial epithelial cells obtained from CF and non-CF patients were differentiated into a mucociliated epithelia in order to assess the effects of our compounds on some key properties of ASL. The treatment of these functional models with non-toxic doses of the synthetic anionophores improved the periciliary fluid composition, reducing the fluid re-absorption, correcting the ASL pH and reducing the viscosity of the mucus, thus representing promising drug candidates for CF therapy.
PB MDPI
SN 1422-0067
YR 2020
FD 2020
LK http://hdl.handle.net/10259/8329
UL http://hdl.handle.net/10259/8329
LA eng
NO This work was financially supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 667079 and from the Italian Cystic Fibrosis Foundation (FFC no. CP/2012 with the contribution of ‘Delegazione FFC di Verona and Imola-Romagna’ and ‘Delegazione FFC di Roma’).
DS Repositorio Institucional de la Universidad de Burgos
RD 09-may-2024