Alteration of Urothelial Inflammation, Apoptosis, and Junction Protein in Patients with Various Bladder Conditions and Storage Bladder Symptoms Suggest Common Pathway Involved in Underlying Pathophysiology.

OBJECTIVE

Lower urinary tract symptoms (LUTS) are common in various bladder disorders. This study investigated urothelial dysfunction and chronic inflammation in the urothelium in different types of lower urinary tract dysfunction (LUTD), which causes bladder storage symptoms.

METHODS

Bladder tissues were obtained from patients with LUTD including 17 with interstitial cystitis/bladder pain syndrome (IC/BPS), 15 with bladder outlet obstruction (BOO), 12 with spinal cord injury (SCI), 12 with recurrent urinary tract infection (UTI), 13 with ketamine related cystitis (KC) and 10 controls. The bladder specimens were investigated using immunofluorescence (IF) staining of the urothelial junction protein E-cadherin and the TUNEL assay for urothelial apoptosis. Mast cell activation was also measured by IF using tryptase for mucosal inflammation. Statistical analysis was performed using the Kruskal-Wallis and Wilcoxon rank-sum test and P-values less than 0.05 were considered significant.

RESULTS

Highly significant increases of mast cell infiltration were observed in patients with KC (7.8 ± 3.7), IC/BPS (4.6 ± 3.0), recurrent UTI (2.4 ± 1.2), SCI (3.7 ± 2.7), and BOO (5.1 ± 2.0) compared with controls (1.3 ± 1.2) (all p < 0.05). Statistically significant increases of apoptotic cells were observed in patients with KC (4.2 ± 1.5), IC/BPS (2.4 ± 1.7), SCI (2.4 ± 1.4), recurrent UTI (1.9 ± 2.4), and BOO (1.2 ± 1.1) compared with controls (0.08 ± 0.3) (all p < 0.05). Significantly decreased expression of E-cadherin in patients with IC/BPS (25.1 ± 16.3), KC (11.0 ± 11.3), and recurrent UTI (26.2 ± 5.0) was found compared to controls (42.4 ± 16.7) and patients with SCI (44.4 ± 18.8) or BOO (42.8 ± 14.3) (all P < 0.05).

CONCLUSION

Increased urothelial inflammation and urothelial cell apoptosis seem to share common pathophysiologies of various LUTDs that cause similar bladder symptoms.