The urothelial fibrogenesis and inflammation cytokines in patients of IC/BPS with different clinical phenotypes and symptom severity

Jhang J1, Lori B2, Jiang Y1, Hsu Y3, Ho H4, Kuo H1

Research Type

Basic Science / Translational

Abstract Category

Pelvic Pain Syndromes / Sexual Dysfunction

Abstract 458
Basic Science: Overactive Bladder and Pain
Scientific Podium Short Oral Session 24
Thursday 30th August 2018
14:22 - 14:30
Hall C
Painful Bladder Syndrome/Interstitial Cystitis (IC) Pathophysiology Basic Science
1. Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan, 2. Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, 3. Department of Pathology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan, 4. Department of Anatomy, Tzu Chi University, Hualien, Taiwan

Jia-Fong Jhang



Hypothesis / aims of study
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.
Study design, materials and methods
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).
Interpretation of results
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.
Concluding message
Our data suggest abnormal fibrogenic activity, impaired tissue healing and increased inflammatory cytokines may involve in the pathogenesis of IC/BPS.
Figure 1
Funding None Clinical Trial No Subjects Human Ethics Committee Research Ethics Committee, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Helsinki Yes Informed Consent Yes
26/02/2021 12:20:58