Higher levels of cell apoptosis and abnormal E-cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome

Abstract

Objective: To investigate the relationships between suburothelial inflammation and urothelial dysfunction in interstitial cystitis/painful bladder syndrome (IC/PBlS).

Materials and methods: Immunofluorescence staining of ki-67 (to assess cell proliferation), junction protein E-cadherin, tryptase (to assess mast cell activation) and TUNEL (to assess urothelial apoptosis) were performed in bladder tissues from 20 patients with IC/PBlS and from 6 control patients. The fluorescence intensity of E-cadherin was measured using the ImageJ method. The percentage of apoptotic cells, proliferated cells and activated mast cells were measured and quantified as positive cells (±SD) per area unit (4 µm(2)).

Results: The ratio of ki-67-positive cells in the bladder tissue of the patients with IC/PBlS was significantly down-regulated compared with that of the control patients (0.559 ± 0.658 vs. 1.23 ± 1.28, P = 0.001). TUNEL staining revealed a significantly higher number of apoptotic cells in the IC/PBlS bladder tissue compared with control bladder tissue (2.26 ± 2.04 v 0.051 ± 0.124, P = 0.000). The tryptase signal was significantly stronger in the IC/PBlS bladder tissue compared with that of control patients (6.16 ± 4.35 v 1.15 ± 0.436, P = 0.000). The apoptotic cell number in IC/PBlS bladder tissue correlated significantly with mast cell activation (P = 0.021). Immunofluorescence also showed a significantly lower distribution of E-cadherin in IC/PBlS bladder tissue compared with that of control patients (8.50 ± 6.83 v 17.2 ± 11.9, P = 0.000). Lower expression of E-cadherin in IC/PBlS bladder tissue was significantly correlated with higher visual analogue pain scores in patients with IC/PBlS (P= 0.008).

Conclusions: The results of the present study suggest that urothelial homeostasis in IC/PBlS bladders was impaired, and abnormal urothelial function was significantly associated with chronic inflammation. The junctions between urothelial cells in IC/PBlS bladders were abnormal, which was associated with the patient's self-report pain scales.