PD19-12 TEMPORAL EFFECTS OF CHRONIC BLADDER OVER-DISTENSION ON HIF-1α AND VEGF EXPRESSION IN MOUSE UROTHELIUM

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I1 Apr 2018PD19-12 TEMPORAL EFFECTS OF CHRONIC BLADDER OVER-DISTENSION ON HIF-1α AND VEGF EXPRESSION IN MOUSE UROTHELIUM Melissa A. Laudano, Marcia Urban-Maldonado, Mia M. Thi, and Sylvia O. Suadicani Melissa A. LaudanoMelissa A. Laudano More articles by this author , Marcia Urban-MaldonadoMarcia Urban-Maldonado More articles by this author , Mia M. ThiMia M. Thi More articles by this author , and Sylvia O. SuadicaniSylvia O. Suadicani More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1002AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Diabetes mellitus (DM) imposes time-dependent changes in bladder physiology. An early increase in mechanical loading due to polyuria followed by the accumulation of oxidative stress products are seen as key factors driving the bladder from a compensated overactive to a decompensated atonic state. In this study we investigated whether chronic mechanical over-distension triggers hypoxic responses in the bladder urothelium and determined if these responses corresponded with the transition from compensated to decompensated state. Hypoxic responses were evaluated by measuring changes in expression levels of the hypoxia inducible factor-1α (HIF-1α) and of the downstream HIF regulated Vascular Endothelial Growth Factor (VEGF). METHODS Studies were performed with 10 week old male C57BL/6 mice treated for 1, 4, 12, 36 weeks with 5% sucrose in the drinking water (diuresis mouse model was used to avoid confounding effects of hyperglycemia), and non-treated age-matched control mice. Void Stain on Paper (VSOP) was used to longitudinally quantify changes in voiding frequency (VF). Bladders were harvested at the end of each time point, the urothelium dissected, and processed for quantification of HIF-1α and VEGF mRNA by real-time quantitative PCR (qPCR). RESULTS HIF-1α and VEGF mRNA expression were upregulated after 1 week of sucrose-induced diuresis (1wk - HIF-1α: 1.85±0.08 and VEGF: 1.57±0.21; mRNA norm. to mean Ctrl value; N = 4, P<0.05), and then progressively decreased (4 wks - HIF-1α: 1.20±0.07 and VEGF 0.80±0.09; N= 4; 12 wks - HIF-1α: 0.73±0.09; P<0.05; VEGF: 0.97±0.11; N = 4) to reach values that were significantly lower or equivalent to controls by 36 weeks (HIF-1α: 0.87±0.05, P<0.05; VEGF: 1.05±0.06; N = 4). Upregulation of HIF-1α and VEGF coincided with emergence of detrusor overactivity (1 wk VF: Ctrl 0.51±0.09 vs Suc-fed 0.95±0.18, N = 6-9, P<0.05) whereas downregulation was seen in conjunction with bladder underactivity (36 wks VF: Ctrl: 0.40±0.08 vs Suc-fed: 0.51±0.12, N=6-9). CONCLUSIONS Chronic bladder over-distension triggers time-dependent changes in HIF-1α and VEGF expression in the bladder urothelium. The early upregulation of HIF-1α and VEGF expression suggests that hypoxic responses may contribute to emergence of detrusor overactivity. In contrast, HIF-1α and VEGF downregulation observed as the bladder transitions to a decompensated state, suggests that factors other than those driven by hypoxia are likely involved in this response. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e400 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Melissa A. Laudano More articles by this author Marcia Urban-Maldonado More articles by this author Mia M. Thi More articles by this author Sylvia O. Suadicani More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...