Partial Bladder Outlet Obstruction in Mice May Cause E-Cadherin Repression through Hypoxia Induced Pathway

No AccessJournal of UrologyInvestigative Urology1 Sep 2014Partial Bladder Outlet Obstruction in Mice May Cause E-Cadherin Repression through Hypoxia Induced Pathway Naoko Iguchi, Amy Hou, Hari K. Koul, and Duncan T. Wilcox Naoko IguchiNaoko Iguchi , Amy HouAmy Hou , Hari K. KoulHari K. Koul , and Duncan T. WilcoxDuncan T. Wilcox View All Author Informationhttps://doi.org/10.1016/j.juro.2014.03.037AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Posterior urethral valves are the most common cause of partial bladder outlet obstruction in the pediatric population. Posterior urethral valves is a devastating clinical problem that ultimately results in urinary incontinence, neurogenic bladder and renal impairment. Despite improvements in medical and surgical management at least a third of patients with this condition progress to end stage renal disease and half will have problems with urinary incontinence. To achieve better understanding of the mechanism associated with clinical events we generated partial bladder outlet obstruction in male mice. In this model we investigated pathological consequences and underlying molecular mechanisms secondary to partial bladder outlet obstruction. Materials and Methods: Five to 8-week-old male C57BL/6 mice were divided into a surgical obstruction group and a sham operated group that served as controls. Bladders and kidneys were harvested from each group 1, 2, 3, 5 and 7 days postoperatively, respectively. We examined histological and biochemical alterations, and further investigated our hypothesis that partial bladder outlet obstruction induces hypoxia activated profibrotic signaling and changes in gene expression in the bladder. Results: Mice with partial bladder outlet obstruction demonstrated significant increases in bladder mass and urinary retention compared to sham operated mice. Obstruction caused fibrosis in the bladder and induced up-regulation of profibrotic genes, hypoxia-inducible factors and epithelial-mesenchymal transition-inducing transcription factors, resulting in E-cadherin down-regulation. Conclusions: Obstruction induced significant histological and molecular alterations, including activation of the hypoxia-inducible factors pathway in the mouse bladder. Activation of epithelial-mesenchymal transition-inducing transcription factors by hypoxia-inducible factors might have an important role in the pathogenesis of partial bladder outlet obstruction. References 1 : Bladder outlet obstruction: etiology and evaluation. Rev Urol2005; 7: S3. Google Scholar 2 : Stromal hyperplasia in male bladders upon loss of transforming growth factor-beta signaling in fibroblasts. J Urol2005; 174: 1704. 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Google Scholar © 2014 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byJiang Y and Kuo H (2018) Urothelial Barrier Deficits, Suburothelial Inflammation and Altered Sensory Protein Expression in Detrusor UnderactivityJournal of Urology, VOL. 197, NO. 1, (197-203), Online publication date: 1-Jan-2017.Iguchi N, Malykhina A and Wilcox D (2016) Inhibition of HIF Reduces Bladder Hypertrophy and Improves Bladder Function in Murine Model of Partial Bladder Outlet ObstructionJournal of Urology, VOL. 195, NO. 4 Part 2, (1250-1256), Online publication date: 1-Apr-2016.Jiang Y, Lee C and Kuo H (2018) Urothelial Dysfunction, Suburothelial Inflammation and Altered Sensory Protein Expression in Men with Bladder Outlet Obstruction and Various Bladder Dysfunctions: Correlation with UrodynamicsJournal of Urology, VOL. 196, NO. 3, (831-837), Online publication date: 1-Sep-2016.Chen L, Yang J, Hu H and Wang Z (2018) Re: Preventive Effect of Hydrogen Water on the Development of Detrusor Overactivity in a Rat Model of Bladder Outlet ObstructionJournal of Urology, VOL. 196, NO. 2, (620-621), Online publication date: 1-Aug-2016.Chen L, Yang J, Xing S and Yang Y (2018) Re: The NLRP3 Inflammasome Mediates Inflammation Produced by Bladder Outlet ObstructionJournal of Urology, VOL. 196, NO. 4, (1323-1324), Online publication date: 1-Oct-2016. Volume 192Issue 3September 2014Page: 964-972Supplementary Materials Advertisement Copyright & Permissions© 2014 by American Urological Association Education and Research, Inc.Keywordsepithelial-mesenchymal transitionurinary bladder neck obstructionanoxiafibrosisgene expressionAcknowledgmentsJoshua Steffan provided technical and editing assistance.MetricsAuthor Information Naoko Iguchi More articles by this author Amy Hou More articles by this author Hari K. Koul More articles by this author Duncan T. Wilcox More articles by this author Expand All Advertisement PDF downloadLoading ...