Previous studies showed unhealthy urothelium inflammation in interstitial cystitis/bladder pain syndrome (IC/BPS). Bladder wall fibrosis was also noted in IC/BPS, especially in the patients with Hunner’s lesion. The aim of current study is to investigate the urothelial fibrogenesis and inflammatory cytokines in patients with IC/BPS.

The patients with IC/BPS who were admitted for cystoscopic hydrodistention were recruited. The symptoms severity was investigated with Interstitial Cystitis Symptoms and Problem Index (ICSI and ICPI), O'Leary-Saint symptom score (OSS), Visual Analogue Scale for pain (VAS) and cystometric bladder capacity (CBC). The patients were classified into IC/BPS with Hunner’s lesion (HIC) and non-Hunner’s lesion IC/BPS (NHIC) groups according to the cystoscopic findings. Random cold-cup biopsies of the posterior bladder wall were obtained during hydrodistention. Western blotting with quantification was used to investigate the fibrogenesis cytokine transforming growth factor beta (TGF-β), fibroblast growth factor receptor (FGFR) 3 and 4 expression in the specimens. The urothelial inflammatory cytokines, including interleukin-1β (IL-1β), macrophage inflammatory protein 2 (MIP-2), intercellular adhesion molecule 1 (ICAM-1) were also investigated with western blotting.  Bladder specimens from female patients with stress urinary incontinence were also obtained for western blotting and were considered as control subjects.

Totally 24 control subjects, 51 non-ulcer IC/BPS and 23 ulcer IC/BPS were enrolled. The patients with non-ulcer IC/BPS was younger than ulcer IC/BPS and control subjects. The urothelium TGF-β was significantly higher in total patients with IC/BPS than that in control subjects, especially in the HIC patients. The urothelium expression of FGFR3 and FGFR4 were significantly higher in control subjects (Table 1). The FGFR3 expression in the urothelium was significantly correlated to FRGR4 (r=0.856, p<0.001), and MIP-2 (r=0.327, p=0.001). The urothelial ICAM-1 expression was significantly correlated to ICSI (r= 0.380, p=0.005), ICPI (r=0.306, p<0.024), OSS (r=0.357, p=0.008) and VAS (r=0.322, p=0.014).

Current study revealed increased fibrogenic cytokine TGF-β in human IC/BPS urothelium. The FGFR, which was associated with tissue healing, was significantly decreased in IC/BPS bladder. Our data suggest increased fibrosis activity and impaired tissue healing in the urothelium may involve in the IC/BPS pathogenesis. The increased urothelial ICAM-1, which was well known for its role in inflammation process, also might impact the pathogenesis and correlate to the IC/BPS clinical symptoms.

Our data suggest abnormal fibrogenic activity, impaired tissue healing and increased inflammatory cytokines may involve in the pathogenesis of IC/BPS.