CFTR correctors suppress Ca²⁺-cAMP signaling and cyst growth in primary cultures of ARPKD cholangiocytes. (PubMed, Cell Calcium) - Sep 25, 2026 - "These changes were accompanied by profound remodeling of intracellular signaling, including elevated resting cytosolic Ca²⁺, an increased thapsigargin-releasable endoplasmic reticulum Ca²⁺ pool, increased STIM1 expression, reduced IP₃ receptor expression, a marked increase in intracellular cAMP, and a switch in adenylyl cyclase isoform expression characterized by increased AC3 and reduced AC6...Treatment with either VX-809 or VX-445 improved many of these abnormalities by increasing CFTR expression, partially restoring PC1 and PC2 expression, attenuating abnormal Ca²⁺ and cAMP signaling, reducing cholangiocyte proliferation and cyst growth, and shifting CFTR membrane distribution toward the WT pattern...These findings identify coordinated remodeling of Ca²⁺- and cAMP-dependent signaling as a central feature of ARPKD cholangiocytes and show that CFTR correctors are associated with improvement of multiple disease-associated pathways...."
Journal • Cystic Fibrosis • Genetic Disorders • Hepatology • Immunology • Nephrology • Polycystic Kidney Disease • Pulmonary Disease • Renal Disease • Respiratory Diseases • CFTR • PKD1 • PKHD1 • STIM1
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Abhishek Sharma; Liudmila Cebotaru; Masoud Afshani; Tanvi Sharma
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