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

Area of Science:

• Urology
• Physiology
• Molecular Biology

Background:

• The cystic fibrosis transmembrane conductance regulator (CFTR) is crucial for epithelial ion transport.
• Its specific role in lower urinary tract physiology, particularly bladder function, is not well understood.

Purpose of the Study:

• To investigate the impact of CFTR deficiency on bladder function.
• To explore alterations in ionic homeostasis and cellular signaling pathways in CFTR-deficient bladders.

Main Methods:

• Evaluation of bladder function in CFTR knockout and wild-type mice using in vivo cystometry and ex vivo detrusor contractility assays.
• Histological, immunofluorescence, electrolyte, and Western blot analyses were performed.
• Assessment of bladder morphology, α-SMA, cytokeratin 20, COX-2, and caspase-9 expression.

Main Results:

• CFTR knockout mice displayed unstable cystometric profiles, irregular voiding, and increased peak voiding pressure.
• Depolarization-induced detrusor contractility was significantly reduced in CFTR-deficient mice.
• Electrolyte imbalance (decreased Na+, Cl-; increased K+), reduced cytokeratin 20, and increased COX-2 and caspase-9 were observed.

Conclusions:

• CFTR deficiency disrupts bladder functional homeostasis.
• Impaired bladder coordination and detrusor excitability result from CFTR deficiency.
• Alterations in ion balance and activation of inflammatory/apoptotic pathways contribute to bladder dysfunction in CFTR deficiency.