Urothelial dysfunction and alternations of sensory protein expressions in bladder mucosa in patients with idiopathic detrusor underactivity

Purpose: Detrusor underactivity (DU) can be observed in many neurogenic condition and myogenic failure. The pathomechanism of DU is indefinite, but impaired bladder sensory pathway affecting the activation of detrusor contraction is considered a possible cause. In addition, urothelial dysfunction and dysregulated protein expression in bladder mucosa are proved in many lower urinary tract diseases. This study investigated the potential urothelial dysfunction and proteins expressed in bladder mucosa in DU patients

Materials and Methods: Bladder wall biopsies were performed in 34 idiopathic DU patients, and 10 controls. Immunofluorescence staining of zona occuldens-1 (ZO-1) and E-cadherin in urothelium, and tryptase and TUNEL (indicating mast cells and apoptotic cells respectively) in suburothelium were performed. Western blotting analysis of proteins in bladder mucosa including P2X3, M2 and M3 muscarinic receptors, β-3 adrenoreceptor, EP3 receptor and endothelial nitric oxide synthase (eNOS) were done. DU patients were compared with controls in the aspects of protein expressions.

Results: Eligible DU patients included 22 women and 12 men with a mean age of 56.3 ± 19.7 years. In immunofluorescence staining, DU patients had a significant lower expression of E-cadherin but not ZO-1 in urothelium, and higher mast cell and apoptotic cell numbers in suburothelium than controls. In Western blotting analysis of bladder mucosa, DU patients had significant lower expressions of M2 and M3 muscarinic receptors, β-3 adrenoreceptor, P2X3 receptor, and eNOS in bladder mucosa than controls but not iNOS or EP3 receptor.

Conclusion: Urothelial dysfunction, increased suburothelial inflammation, and alternations of sensory proteins expression in bladder mucosa in DU patients were found. Impaired urothelial signaling and sensory transduction pathway is a probable cause of DU.