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• W1997200512 abstract "You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2011807 BLADDER EPITHELIAL CELL EXPLANTS FROM INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME PATIENTS EXHIBIT DECREASED AKT/WNT SIGNALING AS COMPARED TO MATCHED CONTROLS Susan Keay and Chen-Ou Zhang Susan KeaySusan Keay Baltimore, MD More articles by this author and Chen-Ou ZhangChen-Ou Zhang Baltimore, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.625AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disorder with bladder epithelial thinning or ulceration, pain, urinary frequency and urgency. Bladder epithelial cells from IC/PBS patients make a glycopeptide antiproliferative factor or “APF” (Neu5Acα2-3Galβ1-3GalNAcα-O-TVPAAVVVA) that binds to CKAP4 and inhibits cell growth. Because the peptide portion of APF is 100% homologous to a segment of frizzled 8, a Wnt receptor, we determined whether IC/PBS explants have evidence for decreased Akt/Wnt signaling, and whether abnormalities in Akt/Wnt signaling could be induced by APF treatment of normal cells. METHODS Primary bladder epithelial explants from 6 IC/PBS patients and 6 age- and gender-matched asymptomatic controls were plated in Minimal Essential Medium with supplements, then cultured in completely defined serum-free medium; additional normal cells were similarly plated but treated with active synthetic APF or inactive unglycosylated control peptide (both from PolyPeptide Laboratories). Gene expression was measured by quantitative real-time polymerase chain reaction. Specific protein expression was determined by Western blot and/or enzyme-linked immunosorbent assay. Autoradiogram bands were quantified by scanning densitometry and normalized to β-actin. Significance of a difference in mean values between groups was determined by two-tailed Student's t-test for each assay, with p<.05 considered significant. RESULTS IC/PBS bladder epithelial cell explants had significant decreases in Akt ser473 and GSK3β ser9 phosphorylation; nuclear β-catenin and JunB protein levels; and cellular MMP2 expression, as compared to matched controls. Similarly, treatment of normal bladder epithelial cells with synthetic APF induced significant changes in phosphorylation or expression of the same cell proteins, as compared to treatment with control peptide. CONCLUSIONS Explanted IC/PBS bladder epithelial cells have decreased Akt/Wnt signaling, resulting in significantly decreased nuclear β-catenin and JunB, plus decreased downstream MMP2 expression. Each of these abnormalities could also be induced in normal cells by APF. As Akt/Wnt signaling and MMP2 expression are important for cell proliferation and epithelial to mesenchymal transition, these findings suggest that inhibition of Akt/Wnt signaling by APF may play a role in the decreased proliferation and altered differentiation of IC/PBS bladder epithelial cells previously noted in several laboratories. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e325 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Susan Keay Baltimore, MD More articles by this author Chen-Ou Zhang Baltimore, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W1997200512 title "807 BLADDER EPITHELIAL CELL EXPLANTS FROM INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME PATIENTS EXHIBIT DECREASED AKT/WNT SIGNALING AS COMPARED TO MATCHED CONTROLS" @default.
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