257 TRPV4 IS INVOLVED IN CELL JUNCTION FORMATION IN THE UROGENITAL TRACT. AN ULTRASTRUCTURAL STUDY

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology I1 Apr 2012257 TRPV4 IS INVOLVED IN CELL JUNCTION FORMATION IN THE UROGENITAL TRACT. AN ULTRASTRUCTURAL STUDY Dick Janssen, Kees Jansen, John Heesakkers, and Jack Schalken Dick JanssenDick Janssen Nijmegen, Netherlands More articles by this author , Kees JansenKees Jansen Nijmegen, Netherlands More articles by this author , John HeesakkersJohn Heesakkers Nijmegen, Netherlands More articles by this author , and Jack SchalkenJack Schalken Nijmegen, Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.314AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Transient receptor potential vanilloid subtype 4 (TRPV4) is a non specific cation channel that is located on the epithelial cell membranes of the urinary bladder, the ureter and the distal section of the kidney tubuli. Transgenic TRPV4 deficient mouse have a phenotype that displays bladder dysfunction. Therefore, TRPV4 channels are being investigated as a mechanoreceptor in the bladder and as a potential pharmacological target for OAB. Besides this, numerous TRP-channels have recently been associated with carcinogenesis. Previous research has demonstrated a molecular connection between TRPV4 and barrier forming Adherence Junctions (AJ's) in all above mentioned tissues. Other groups have shown that the skin epithelium of TRPV4 deficient mice have an abnormal cell junction formation. The aim of this study is to investigate cell junction formation in the urogenital tract of humans and in TRPV4 knockout mice. METHODS The location of TRPV4, AJ's and Tight Junctions (TJ) was investigated with immunofluorescence assays, Western blotting and qPCR techniques on non cancerous tissue sections from human cystectomies (n=4), ureterectomies (n=1), nefrectomies (n=2) and kidney and bladder tissues from wild type and TRPV4 −/− mice. Subsequent evaluation of epithelial cell junctions (AJ and TJ) was investigated in bladder tissues from wild type and TRPV4 −/− mice with Transmission Electron Microscopy (TEM). RESULTS TRPV4 co localizes with adherence junctions throughout the urogenital tract (fig; top). Immunofluorescence assays demonstrated a qualitative and quantitative reduction of cell junction formation (both AJ and TJ) in TRPV4 −/− kidney and bladder epithelia (fig; bottom A,B). TEM evaluation confirmed these results and showed a remarkable increase in intercellular space between adjacent urothelial cells of the TRPV4 −/− mouse bladder (fig; bottom C). CONCLUSIONS TRPV4 channels are connected to epithelial adherence junctions throughout the urogenital tract and plays a role in cell junction formation. These result suggest that TRPV4 channels, besides being important for sensory functions, is also involved in epithelial barrier formation. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e104-e105 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dick Janssen Nijmegen, Netherlands More articles by this author Kees Jansen Nijmegen, Netherlands More articles by this author John Heesakkers Nijmegen, Netherlands More articles by this author Jack Schalken Nijmegen, Netherlands More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...