A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study
<p>Abstract</p> <p>Background</p> <p>Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder disorder with bladder epithelial thinning or ulceration, pain, urinary frequency and urgency. There is no reliably effective therapy for IC/PBS, and no gene...
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| Format: | Article |
| Language: | English |
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BMC
2012-06-01
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| Series: | BMC Urology |
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| Online Access: | http://www.biomedcentral.com/1471-2490/12/17 |
| _version_ | 1818808610030878720 |
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| author | Keay Susan Leitzell Samantha Ochrzcin Ashley Clements George Zhan Min Johnson David |
| author_facet | Keay Susan Leitzell Samantha Ochrzcin Ashley Clements George Zhan Min Johnson David |
| author_sort | Keay Susan |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder disorder with bladder epithelial thinning or ulceration, pain, urinary frequency and urgency. There is no reliably effective therapy for IC/PBS, and no generally accepted animal model for the disorder in which potential therapies can be tested. Bladder epithelial cells from IC/PBS patients make a small glycopeptide antiproliferative factor or "APF" that inhibits proliferation, decreases tight junction protein expression, increases paracellular permeability, and induces changes in gene expression of bladder epithelial cells <it>in vitro</it> that mimic abnormalities in IC/PBS patient biopsy specimens <it>in vivo</it>. We therefore determined the ability of a synthetic APF derivative to inhibit bladder epithelial repair in mice.</p> <p>Methods</p> <p>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 <it>as</it>-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.</p> <p>Results</p> <p>Bladder epithelial repair was significantly attenuated in <it>as</it>-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 <it>as</it>-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 <it>as</it>-APF-treated mice as compared to mice in either control group by day 7 (UPIII) or day 14 (ZO-1).</p> <p>Conclusions</p> <p>This model demonstrates <it>in vivo</it> effects of <it>as</it>-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.</p> |
| first_indexed | 2024-12-18T19:44:17Z |
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| id | doaj.art-dfa8d6f610ee4d6ba99618f6317a0a18 |
| institution | Directory Open Access Journal |
| issn | 1471-2490 |
| language | English |
| last_indexed | 2024-12-18T19:44:17Z |
| publishDate | 2012-06-01 |
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| spelling | doaj.art-dfa8d6f610ee4d6ba99618f6317a0a182022-12-21T20:55:21ZengBMCBMC Urology1471-24902012-06-011211710.1186/1471-2490-12-17A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot studyKeay SusanLeitzell SamanthaOchrzcin AshleyClements GeorgeZhan MinJohnson David<p>Abstract</p> <p>Background</p> <p>Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder disorder with bladder epithelial thinning or ulceration, pain, urinary frequency and urgency. There is no reliably effective therapy for IC/PBS, and no generally accepted animal model for the disorder in which potential therapies can be tested. Bladder epithelial cells from IC/PBS patients make a small glycopeptide antiproliferative factor or "APF" that inhibits proliferation, decreases tight junction protein expression, increases paracellular permeability, and induces changes in gene expression of bladder epithelial cells <it>in vitro</it> that mimic abnormalities in IC/PBS patient biopsy specimens <it>in vivo</it>. We therefore determined the ability of a synthetic APF derivative to inhibit bladder epithelial repair in mice.</p> <p>Methods</p> <p>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 <it>as</it>-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.</p> <p>Results</p> <p>Bladder epithelial repair was significantly attenuated in <it>as</it>-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 <it>as</it>-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 <it>as</it>-APF-treated mice as compared to mice in either control group by day 7 (UPIII) or day 14 (ZO-1).</p> <p>Conclusions</p> <p>This model demonstrates <it>in vivo</it> effects of <it>as</it>-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.</p>http://www.biomedcentral.com/1471-2490/12/17Interstitial cystitisPainful bladder syndromeMouse model |
| spellingShingle | Keay Susan Leitzell Samantha Ochrzcin Ashley Clements George Zhan Min Johnson David A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study BMC Urology Interstitial cystitis Painful bladder syndrome Mouse model |
| title | A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study |
| title_full | A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study |
| title_fullStr | A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study |
| title_full_unstemmed | A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study |
| title_short | A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study |
| title_sort | mouse model for interstitial cystitis painful bladder syndrome based on apf inhibition of bladder epithelial repair a pilot study |
| topic | Interstitial cystitis Painful bladder syndrome Mouse model |
| url | http://www.biomedcentral.com/1471-2490/12/17 |
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