Hypothesis / aims of study
The pathogenesis in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and recurrent urinary tract infection (rUTI) is still unclear. Previous studies revealed urothelium denudation and barrier function impairment in both IC/BPS and rUTI bladder. However, the cause of urothelium barrier function defect is still known. The urothelial interstitial cells function, especially in cell regeneration and tissue healing activity impairment, might have an impact on the pathogenesis of IC/BPS and rUTI. The aim of current study is to investigate the interstitial cells function and urothelium regeneration markers expression in the patients with IC/BPS and rUTI.
Study design, materials and methods
The patients with IC/BPS and rUTI who were admitted to our ward for intravesical injection treatment were recruited. The patients were asked to provide bladder specimens. Before the injection, the cold-cup bladder biopsy was performed under general anesthesia. The patients with stress urinary incontinence who were admitted for anti-incontinence surgery were also asked to provide bladder tissue during the surgery as control subjects. The patients with current pyuria or acute bacteria cystitis were excluded from this study. The bladder specimens were sent to our lab for western blot and immunochemical staining. The urothelium interstitial cell marker c-kit, CD34, and the tissue repair factor podoplanin expression levels were investigated with western blot. The western blot results in patients and control subjects were compared.
Results
A total of 10 control subjects(59.6±10.8 years old), 10 rUTI(68.8±9.8 years old) and 18 IC/BPS patients (54.8±16.7 years old, 5 patients with Hunner’s lesion and the other 13 patients were non-Hunner IC/BPS) were enrolled and provided bladder specimens. The immunochemical staining revealed the most of the CD34 expression was located in superficial lamina propria, while most of the c-kit expression was located in the deep lamina propria (Fig. 1). The western blot quantification result revealed the level of urothelium podoplanin expression in patients with IC/BPS was significantly lower than that in control subjects (p=0.008, Table 1). The interstitial cell marker CD34 expression in IC/BPS urothelium also was marginally lower than that in the control subjects (p=0.053), while the c-kit expression is not different. In the patients with rUTI, both the levels of CD-34, c-kit and podoplanin expression in the urothelium were not significantly different from those in the control subjects.
Interpretation of results
This is the first study to investigate the interstitial cell marker CD34 and tissue healing marker podoplanin expression in human IC/BPS and rUTI bladders. The western blot quantification results revealed the level of urothelial interstitial cells marker c-kit expression was not different between control, IC/BPS and rUTI. However, the other interstitial cells marker CD34, which is considered as a marker of cell regeneration activity, was marginally lower in the IC/BPS than that in control. The urothelial tissue healing factor podoplanin expression in the IC/BPS bladder was lower than that in control. Our immunochemical staining showed the CD34 expression located in superficial lamina proria, and the c-kit expression located in deep lamina proria. This finding was similar to previous animal bladder interstitial cells study. The CD34 positive cells expression near the urothelium basement membrane might be associated with uroepithelial cells regeneration. Our results revealed downregulation of podoplanin and CD34 in IC/BPS bladder. This finding suggested the urothelial cell healing and regeneration function impairment in bladder might involve the pathogenesis of IC/BPS. Our study now was limited by small case number, and need further investigation.