MP49-16 IMPAIRED UROTHELIAL BARRIER FUNCTION INDUCED LOWER URINARY TRACT DYSFUNCTION BY PROTEASE-ACTIVATED RECEPTER 2 ACTIVATION

Abstract

You have accessJournal of UrologyCME1 May 2022MP49-16 IMPAIRED UROTHELIAL BARRIER FUNCTION INDUCED LOWER URINARY TRACT DYSFUNCTION BY PROTEASE-ACTIVATED RECEPTER 2 ACTIVATION Hidenori Akaihata, Yusuke Hakozaki, Hiroki Natsuya, Tomoyuki Kumekawa, Shunsuke Yoshioka, Hitomi Imai, Akifumi Onagi, Kanako Matsuoka, Tomoyuki Koguchi, Junya Hata, Yuichi Sato, Masao Kataoka, and Yoshiyuki Kojima Hidenori AkaihataHidenori Akaihata More articles by this author , Yusuke HakozakiYusuke Hakozaki More articles by this author , Hiroki NatsuyaHiroki Natsuya More articles by this author , Tomoyuki KumekawaTomoyuki Kumekawa More articles by this author , Shunsuke YoshiokaShunsuke Yoshioka More articles by this author , Hitomi ImaiHitomi Imai More articles by this author , Akifumi OnagiAkifumi Onagi More articles by this author , Kanako MatsuokaKanako Matsuoka More articles by this author , Tomoyuki KoguchiTomoyuki Koguchi More articles by this author , Junya HataJunya Hata More articles by this author , Yuichi SatoYuichi Sato More articles by this author , Masao KataokaMasao Kataoka More articles by this author , and Yoshiyuki KojimaYoshiyuki Kojima More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002624.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recently, attention has focused on the association between urothelial barrier dysfunction and lower urinary tract dysfunction (LUTD). Uroplakin (UP) is critical to normal urothelial barrier function. Some studies reported that UPs defects lead to abnormal voiding patterns. It was also reported that impairing UP II causes mast cell infiltration in the bladder and that mast cell contributed to bladder hyperactivity. Mast cell tryptase (MCT) can regulate neuronal activity by cleaving protease-activated recepter 2 (PAR2), which is expressed on C-fiber. On the other hands, the mechanisms underlying LUTD caused by chronic ischemia are not completely known. This study aimed to investigate the effects of chronic ischemia on UPs and mast cell in the bladder using a rat model of chronic bladder ischemia (CBI). METHODS: Adult male Sprague-Dawley rats (16 weeks old) were divided into two groups (control and CBI; n=10 each). The CBI group received balloon endothelial injury of bilateral iliac arteries and a 2% cholesterol diet for 8 weeks to induce chronic ischemia. The control group received regular diet for 8 weeks. After monitoring urine output for 24 h, bladders were harvested. Bladder was processed for immunohistochemical staining and methylene blue staining. We used western blotting to measure expressions of UPs(UP Ia, UP Ib, UP II, UP III) in the bladder of this rat model to examine urothelial barrier function. The expression of MCT and PAR2 were also measured to evaluate C-fiber activation by mast cell. RESULTS: Metabolic cage studies showed that mean voided volumes were significantly smaller in the CBI (1.46±0.33 ml) than in the control (1.01±0.21 ml; P=0.001). In western blot analysis, UP II expression was significantly decreased (P=0.011) in the CBI compared with the control. With immunohistochemical staining, UP II-positive cells are located mostly. The percentage of UP II-positive cells on urothelium was significantly lower in the CBI (63.0±0.11%) than in the control (92.1±0.1%, P<0.001). The expression of MCT (P=0.024) and PAR2 (P=0.021) were significantly increased in the CBI compared with the control in western blot analysis. The methylene blue staining showed the number of mast cell was significantly more in the CBI than in the control (P=0.034). CONCLUSIONS: Chronic ischemia might impair urothelial barrier function through reduced expression of UP II in urothelium. Urothelial barrier dysfunction contributed to mast cell infiltration and increased PAR2 on C-fiber, resulting PAR2 activation by MCT. The PAR2 activation may induce LUTD by stimulating C fiber in rat model of chronic bladder ischemia. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e860 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hidenori Akaihata More articles by this author Yusuke Hakozaki More articles by this author Hiroki Natsuya More articles by this author Tomoyuki Kumekawa More articles by this author Shunsuke Yoshioka More articles by this author Hitomi Imai More articles by this author Akifumi Onagi More articles by this author Kanako Matsuoka More articles by this author Tomoyuki Koguchi More articles by this author Junya Hata More articles by this author Yuichi Sato More articles by this author Masao Kataoka More articles by this author Yoshiyuki Kojima More articles by this author Expand All Advertisement PDF DownloadLoading ...