198 TRPV4 IN STRETCH SENSATION. TRPV4 IN THE UROTHELIUM OF HUMAN BLADDER, KIDNEY & URETER COLOCALIZES WITH ADHERENCE JUNCTIONS

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology I1 Apr 2010198 TRPV4 IN STRETCH SENSATION. TRPV4 IN THE UROTHELIUM OF HUMAN BLADDER, KIDNEY & URETER COLOCALIZES WITH ADHERENCE JUNCTIONS Dick Janssen, Jack Schalken, Kees Janssen, and John Heesakkers Dick JanssenDick Janssen More articles by this author , Jack SchalkenJack Schalken More articles by this author , Kees JanssenKees Janssen More articles by this author , and John HeesakkersJohn Heesakkers More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.254AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We investigated the location of TRPV4 in the urothelium of the kidney, ureter & bladder. TRPV4 is a cation channel that is located on the cell-membranes of the bladder urothelium. Accumulating evidence proves that TRPV4-channels function as mechanoreceptors. This has led to the hypothesis that TRPV4 is involved in bladder filling sensation. It could also be involved in diseases that cause voiding dysfunction (OAB/PBS). In recent immunohistochemistry experiments we have proven a co-localization between TRPV4 and adherence junctions (AJ's) in the urothelium of the human bladder. AJ's have an intra- and an extracellular domain. The first is connected to the actin cytoskeleton. The second anchors neighbouring urothelial cells to each other. Together, this forms a structural network that is able to transmit the mechanical forces that originate during bladder filling and is therefore a good location to measure stretch. The aim of our study was to further explore the co-localization of TRPV4 & AJ's in the urothelium of the human urogenital tract (kidney, ureter, bladder). Secondarily, we wanted to confirm this co-localization in another species (mouse). METHODS We used tissue from healthy sections of cystectomy & nefrectomy patients. Bladders and kidneys obtained from normal & TRPV4 -/- mice were used as positive and negative controls. Tissue was prepared for immunohistochemistry. After incubation with primary antibodies for TRPV4 & E-cadherine and secundary antibodies Alexa's & DAPI, samples were evaluated with epifuorescent microscope. Western blotting and immunoprecipitations were done on human, mouse and TRPV4-/- mouse kidneys. Besides the previous antibodies, also antibodies for α-catenin & β-catenin were used. RESULTS TRPV4 was detected in human & mouse urothelium of bladder, ureter & kidney (only in distal tubuli & collecting ducts) and co-localized with AJ's in all tissues examined. Immunoprecipitation experiments revealed that TRPV4 is bound to α-catenin. This connection enables TRPV4 to measure stretch. CONCLUSIONS TRPV4 is connected to the intracellular domain of AJ's in the urothelium of the bladder, the ureter & the distal tubuli of the kidney. These findings suggest that TRPV4 is involved in the sensation of stretch in the urothelium. Nijmegen, Netherlands© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e78 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dick Janssen More articles by this author Jack Schalken More articles by this author Kees Janssen More articles by this author John Heesakkers More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...