Interstitial cystitis antiproliferative factor (APF) as a cell-cycle modulator.

Hani H Rashid,Susan K Keay,Chen-Ou Zhang,Edward M Messing,Jay E Reeder,Mary J O'Connell

doi:10.1186/1471-2490-4-3

Abstract

BackgroundInterstitial cystitis (IC) is a chronic bladder disorder of unknown etiology. Antiproliferative factor (APF), a peptide found in the urine of IC patients, has previously been shown to decrease incorporation of thymidine by normal bladder epithelial cells. This study was performed to determine the effect of APF on the cell cycle of bladder epithelial cells so as to better understand its antiproliferative activity.MethodsExplant cultures from normal bladder biopsy specimens were exposed to APF or mock control. DNA cytometry was performed using an automated image analysis system. Cell cycle phase fractions were calculated from the DNA frequency distributions and compared by two-way analysis of variance (ANOVA).ResultsAPF exposure produced statistically significant increases in the proportion of tetraploid and hypertetraploid cells compared to mock control preparations, suggesting a G2 and/or M phase cell cycle block and the production of polyploidy.ConclusionsAPF has a specific effect on cell cycle distributions. The presence of a peptide with this activity may contribute to the pathogenesis of interstitial cystitis through disruption of normal urothelial proliferation and repair processes.

Highlights

Interstitial cystitis (IC) is a chronic bladder disorder of unknown etiology
Primary cultures of normal bladder epithelium were treated in replicate with 10, 20 or 50 μl of Antiproliferative factor (APF) or mock preparation per 3 ml well
These findings suggest the intriguing possibilities that bladder epithelial abnormalities in IC may be caused by APF, and that replacement of specific factor(s) altered by APF may result in normalization of bladder epithelial cell growth [16]

Summary

Introduction

Antiproliferative factor (APF), a peptide found in the urine of IC patients, has previously been shown to decrease incorporation of thymidine by normal bladder epithelial cells. APF, a peptide purified from the urine of IC patients has been shown to decrease incorporation of thymidine by bladder epithelial cells, decrease levels of urinary heparin-binding epidermal growth factor-like growth factor (HB-EGF) and increase levels of epidermal growth factor (EGF) in vitro which reflects altered levels of these growth factors seen in (page number not for citation purposes). This study was performed to determine the effect of APF on the cell cycle of bladder epithelial cells so as to better understand its antiproliferative activity

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