2026-11-02T00:27:05Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/83292024-01-15T10:40:05Zcom_10259_3592com_10259_3591com_10259.4_106com_10259_2604com_10259_3924com_10259_5086col_10259_3930col_10259_3925

00925njm 22002777a 4500 dc Gianotti, Ambra author Capurro, Valeria author Delpiano, Livia author Mielczarek, Marcin author García Valverde, María author Carreira Barral, Israel author Ludovico, Alessandra author Fiore, Michele author Baroni, Debora author Moran, Óscar author Quesada Pato, Roberto author Caci, Emanuela author 2020 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. 1422-0067 http://hdl.handle.net/10259/8329 10.3390/ijms21041488 1422-0067 Cystic fibrosis Anionophore Bronchial epithelial cells culture Ion transport Periciliar mucus properties Small Molecule Anion Carriers Correct Abnormal Airway Surface Liquid Properties in Cystic Fibrosis Airway Epithelia