WNK Inhibition Increases Surface Liquid pH and Host Defense in Cystic Fibrosis Airway Epithelia.

ABSTRACT: In cystic fibrosis (CF), reduced HCO₃^- secretion acidifies the airway surface liquid (ASL), and the acidic pH disrupts host defenses. Thus, understanding the control of ASL pH (pH_ASL) in CF may help identify novel targets and facilitate therapeutic development. In diverse epithelia, the WNK (with-no-lysine [K]) kinases coordinate HCO₃^- and Cl^- transport, but their functions in airway epithelia are poorly understood. Here, we tested the hypothesis that WNK kinases regulate CF pH_ASL. In primary cultures of differentiated human airway epithelia, inhibiting WNK kinases acutely increased both CF and non-CF pH_ASL. This response was HCO₃^- dependent and involved downstream SPAK/OSR1 (Ste20

SUBMITTER: Rehman T 

PROVIDER: S-EPMC9564924 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature