Small Molecule Anion Carriers Correct Abnormal Airway Surface Liquid Properties in Cystic Fibrosis Airway Epithelia

International Journal of Molecular Sciences

Marcin Mielczarek¹  Israel Carreira-Barral¹  María García-Valverde¹  Roberto Quesada¹  Oscar Moran²  Michele Fiore²  Alessandra Ludovico²  Debora Baroni²  Emanuela Caci³  Ambra Gianotti³  Valeria Capurro³  Livia Delpiano³ 

[1] Departamento de Química, Facultad de Ciencias, Universidad de Burgos, 09001 Burgos, Spain;Istituto di Biofisica, Consiglio Nazionale Delle Ricerche (CNR), 16149 Genova, Italy;UOC Genetica Medica, IRCSS Istituto Giannina Gaslini, 16145 Genova, Italy;

关键词: cystic fibrosis;    anionophore;    bronchial epithelial cells culture;    ion transport;    periciliar mucus properties;   

DOI  :  10.3390/ijms21041488

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown