CFTR Deficiency Disrupts Bladder Function Through Ion Imbalance and Inflammatory-Apoptotic Signaling

The cystic fibrosis transmembrane conductance regulator (CFTR) is a key determinant of epithelial ion transport; however, its role in lower urinary tract physiology remains unclear. This study investigated whether CFTR deficiency disrupts bladder function by altering ionic homeostasis and downstream cellular signaling. Bladder function was evaluated in 12-month-old CFTR knockout (Cftr^-/^-) and wild-type mice (n = 8/group) using in vivo cystometry and ex vivo detrusor contractility assays, in addition to histological, immunofluorescence, electrolyte, and Western blot analyses. Cftr^-/^- mice exhibited unstable cystometric profiles with irregular voiding cycles and significantly increased peak voiding pressure, indicating impaired bladder coordination. In contrast, depolarization-induced detrusor contractility was markedly reduced (0.3855 g vs. 1.908 g in wild type), despite preserved bladder morphology and unchanged α-SMA expression. CFTR deficiency was further associated with selective electrolyte imbalance (decreased Na⁺ and Cl^-, increased K⁺). At the molecular level, reduced cytokeratin 20 expression (p < 0.01) suggested urothelial impairment, whereas increased COX-2 (p < 0.05) and caspase-9 (p < 0.01) indicated activation of inflammatory and apoptotic pathways. Collectively, these findings demonstrate that CFTR deficiency disrupts bladder functional homeostasis through integrated effects on ion balance, detrusor excitability and cellular signaling.