The F508del-CFTR trafficking correctors elexacaftor and tezacaftor are CFTR-independent Ca²⁺-mobilizing agonists normalizing abnormal Ca²⁺ levels in human airway epithelial cells.

ABSTRACT:

Background

Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel. For people with CF (pwCF) affected by the most common pathogenic variant F508del, a tritherapy, named Trikafta/Kaftrio (ETI: elexacaftor (VX-445) /tezacaftor (VX-661) / ivacaftor (VX-770)) was successfully developed. However, in CF airway epithelial cells the calcium homeostasis is also disturbed; it is observed an increased calcium mobilization in CF cells compared to non-CF cells. Here, we studied the effects of ETI on intracellular calcium levels in F508del-CFTR airway epithelial cells to determine whether these compounds, individually or collectively, could normalize intracellular calcium levels.

Methods

We measured intracell

SUBMITTER: Leveque M 

PROVIDER: S-EPMC11660580 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature