摘要
No AccessJournal of UrologyAdult Urology1 Jan 2017Urothelial Barrier Deficits, Suburothelial Inflammation and Altered Sensory Protein Expression in Detrusor Underactivity Yuan-Hong Jiang and Hann-Chorng Kuo Yuan-Hong JiangYuan-Hong Jiang More articles by this author and Hann-Chorng KuoHann-Chorng Kuo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.07.071AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The pathophysiology of detrusor underactivity remains unclear and impaired bladder afferent function is considered one of the important etiologies. We investigated urothelial barrier deficits, suburothelial inflammation and sensory proteins expressed in the bladder mucosa of patients with detrusor underactivity. Materials and Methods: Bladder mucosa biopsies were performed in 34 patients with videourodynamic proven detrusor underactivity as the study group and in 10 women with stress urinary incontinence as controls. The expression of zona occuldens-1, E-cadherin in the urothelium, tryptase and apoptosis levels in the suburothelium, β3-adrenoceptor, M2 and M3 muscarinic receptors, P2X3 receptor, and inducible and endothelial nitric oxide synthase were compared between study patients and controls. Results: Study patients included 22 women and 12 men with a mean ± SD age of 56.3 ± 19.7 years, of whom 15 had a history of diabetes. Study patients had significantly lower E-cadherin expression, and a higher number of mast cells and apoptotic cells than controls. Additionally, lower expression of M2 and M3 muscarinic receptors, P2X3 receptors and endothelial nitric oxide synthase was detected in study patients but higher expression of β3-adrenoceptor. In study patients a positive correlation was noted between tryptase and apoptosis levels (r = 0.527) and between the expression of M2 muscarinic receptor and P2X3 receptor (r = 0.403). However, β3-adrenoceptor expression negatively correlated with E-cadherin expression (r = –0.490, each p <0.05). Conclusions: Urothelial dysfunction, increased suburothelial inflammation and altered sensory protein expressions in bladder mucosa were prominent in patients with detrusor underactivity. Impaired urothelial signaling and sensory transduction pathways appear to reflect the pathophysiology of detrusor underactivity. References 1 : Detrusor underactivity: a plea for new approaches to a common bladder dysfunction. Neurourol Urodyn2011; 30: 723. Google Scholar 2 : The other bladder syndrome: underactive bladder. Rev Urol2013; 15: 11. Google Scholar 3 : Aging and the underactive detrusor: a failure of activity or activation?. Neurourol Urodyn2010; 29: 408. Google Scholar 4 : The overactive bladder progression to underactive bladder hypothesis. Int Urol Nephrol2014; 46: S23. Google Scholar 5 : Urothelial signaling. Physiol Rev2014; 93: 653. Google Scholar 6 : Beta3-adrenoceptor agonists: possible role in the treatment of overactive bladder. Korean J Urol2010; 51: 811. Google Scholar 7 : Higher levels of cell apoptosis and abnormal E-cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome. BJU Int2011; 108: E136. Google Scholar 8 : Differences in mast cell infiltration, E-cadherin, and zonula occludens-1 expression between patients with overactive bladder and interstitial cystitis/bladder pain syndrome. Urology2012; 80: 225.e13. Google Scholar 9 : Urothelial dysfunction and chronic inflammation in patients with spinal cord injuries at different levels and correlation with urodynamic findings. Neurourol Urodyn2015; 34: 757. Google Scholar 10 : Voiding dysfunction due to detrusor underactivity: an overview. Nat Rev Urol2014; 11: 454. Google Scholar 11 : Functional consequences of chronic bladder ischemia. Neurourol Urodyn2014; 33: 54. Google Scholar 12 : Chapter 2: pathophysiology of neurogenic detrusor overactivity and the symptom complex of “overactive bladder”. Neurourol Urodyn2014; 33: S6. Google Scholar 13 : Muscarinic and purinergic receptor expression in the urothelium of rats with detrusor overactivity induced by bladder outlet obstruction. BJU Int2008; 101: 371. Google Scholar 14 : Urothelial dysfunction, suburothelial inflammation, and altered sensory protein expression in men with bladder outlet obstruction and various bladder dysfunctions: correlation with urodynamics. J Urol2016; 196: 831. Abstract, Google Scholar 15 : The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn2002; 21: 167. Google Scholar 16 : Techniques of image analysis for quantitative immunohistochemistry. Rocz Akad Med Bialymst2004; 49: 155. Google Scholar 17 : New pharmacologic targets for the treatment of the overactive bladder: an update. Urology2004; 63: 32. Google Scholar 18 : Botulinum toxin A detrusor injections reduce postsynaptic muscular M2, M3, P2X2, and P2X3 receptors in children and adolescents who have neurogenic detrusor overactivity: a single-blind study. Urology2013; 81: 1052. Google Scholar 19 : Bladder activation: afferent mechanisms. Urology2002; 59: 43. Google Scholar 20 : A new look at detrusor underactivity: impaired contractility versus afferent dysfunction. Curr Urol Rep2009; 10: 347. Google Scholar 21 : Activation of muscarinic receptors in rat bladder sensory pathways alters reflex bladder activity. J Neurosci2008; 28: 1977. Google Scholar 22 : Physiologic role of nitric oxide and nitric oxide synthase in female lower urinary tract. Curr Opin Obstet Gynecol2004; 16: 423. Google Scholar 23 : Effect of detrusor overactivity on the expression of aquaporins and nitric oxide synthase in rat urinary bladder following bladder outlet obstruction. Can Urol Assoc J2013; 7: E268. Google Scholar 24 : Inducible nitric oxide synthase promotes pathophysiological consequences of experimental bladder outlet obstruction. J Urol2013; 169: 1569. Google Scholar 25 : Altered neuronal and endothelial nitric oxide synthase expression in the bladder and urethra of cyclophosphamide-treated rats. Nitric Oxide2014; 39: 8. Google Scholar 26 : Expression of nitric oxide synthase and aquaporin-3 in cyclophosphamide treated rat bladder. Int Neurourol J2011; 14: 149. Google Scholar 27 : Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer2002; 2: 442. Google Scholar 28 : Partial bladder outlet obstruction in mice may cause E-cadherin repression through hypoxia induced pathway. J Urol2014; 192: 964. Link, Google Scholar 29 : Diabetic cystopathy: a review. J Diabetes2015; 7: 442. Google Scholar 30 : Alteration of M(3) subtype muscarinic receptors in the diabetic rat urinary bladder. Pharmacology2002; 64: 148. Google Scholar © 2017 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byCho K, Koh J, Choi J and Kim J (2017) Changes in Adenosine Triphosphate and Nitric Oxide in the Urothelium of Patients with Benign Prostatic Hyperplasia and Detrusor UnderactivityJournal of Urology, VOL. 198, NO. 6, (1392-1396), Online publication date: 1-Dec-2017.Smith J (2016) This Month in Adult UrologyJournal of Urology, VOL. 197, NO. 1, (1-3), Online publication date: 1-Jan-2017. Volume 197Issue 1January 2017Page: 197-203 Advertisement Copyright & Permissions© 2017 by American Urological Association Education and Research, Inc.Keywordsurinary bladder neck obstructionproteininflammationmuscle contractionafferent pathwaysMetricsAuthor Information Yuan-Hong Jiang More articles by this author Hann-Chorng Kuo More articles by this author Expand All Advertisement PDF downloadLoading ...