A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study

The bladder epithelium of female CBA/J mice was stripped by transurethral infusion of 3% acetic acid, and mice were subsequently treated daily with one of three intravesical treatments [synthetic as-APF, inactive unglycosylated control peptide, or phosphate buffered saline carrier (PBS)] for 1–21？days. Fixed bladder sections were either stained with haematoxylin and eosin for determination of epithelial area by image analysis, or incubated with anti-uroplakin III (UPIII) or anti-zonula occludens type 1 (ZO-1) antibodies for immunofluorescence microscopy. Epithelial measurement data were analyzed by a two-way analysis of variance (ANOVA); post hoc comparisons of multiple groups were carried out using the Tukey-Kramer method.Bladder epithelial repair was significantly attenuated in as-APF-treated mice as compared to control mice on days 3–21 (p？<？0.05); the mean epithelial/total area over all measured days was also significantly lower in as-APF-treated mice vs. mice in either control group by post hoc analysis (p？<？0.0001 for both comparisons). UPIII and ZO-1 expression was also decreased in as-APF-treated mice as compared to mice in either control group by day 7 (UPIII) or day 14 (ZO-1).This model demonstrates in vivo effects of as-APF which abrogates bladder epithelial repair and expression of UPIII and ZO-1 in CBA/J mice following transurethral acetic acid infusion. As bladder epithelial thinning, decreased UPIII expression, and decreased ZO-1 expression are histopathologic features of IC/PBS patient biopsies, this model may be useful for studying the pathophysiology of IC/PBS and the effect of potential therapies.Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic illness characterized by bladder epithelial thinning or ulceration, pain, urinary frequency and urgency [1-3]. The etiology of IC/PBS remains unknown, and no treatment is reliably effective. Therefore, a greater understanding of the pathogenesis of this debilitating chronic painful bladd