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 K ruskal– W allis and W ilcoxon 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 LUTD s that cause similar bladder symptoms.