Defective CFTR modulates mechanosensitive channels TRPV4 and PIEZO1 and drives endothelial barrier failure.

ABSTRACT: Cystic fibrosis (CF) is a genetic disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite reports of CFTR expression on endothelial cells, pulmonary vascular perturbations, and perfusion deficits in CF patients, the mechanism of pulmonary vascular disease in CF remains unclear. Here, our pilot study of 40 CF patients reveals a loss of small pulmonary blood vessels in patients with severe lung disease. Using a vessel-on-a-chip model, we establish a shear-stress-dependent mechanism of endothelial barrier failure in CF involving TRPV4, a mechanosensitive channel. Furthermore, we demonstrate that CFTR deficiency downregulates the function of PIEZO1, another mechanosensitive channel involved in angiogenesis and wound repair, and exacerbates l

SUBMITTER: Amoakon JP 

PROVIDER: S-EPMC11382128 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature