TRPV4 channels in the human urogenital tract play a role in cell junction formation and epithelial barrier

Acta Physiol (Oxf). 2016 Sep;218(1):38-48. doi: 10.1111/apha.12701. Epub 2016 May 25.

Abstract

Aim: The molecular interactions between transient receptor potential vanilloid subtype 4 channels (TRPV4) and cell junction formation were investigated in the human and mouse urogenital tract.

Materials and methods: A qualitative study was performed to investigate TRPV4 channels, adherence junctions (AJs) and tight junctions (TJs) in kidney, ureter and bladder tissues from humans and wild-type and transgenic TRPV4 knockout (-/-) mice with immunohistochemistry, Western blotting, immunoprecipitation and reverse trasnscription-PCR. Cell junction formation in the wild-type and TRPV4 knockout (-/-) mouse was evaluated with immunohistochemistry and transmission electron microscope (TEM) techniques.

Results: TRPV4 channels are predominantly located in membranes of epithelial cells of the bladder, ureter and the collecting ducts of the kidney. There is a molecular interaction between the TRPV4 channel and the AJ. TEM evaluation showed that AJ formation is disrupted in the TRPV4 -/- mouse resulting in deficient intercellular connections and integrity of the epithelium.

Conclusions: TRPV4 is believed to be a mechanoreceptor in the bladder. This study demonstrates that TRPV4 is also involved in intercellular connectivity and structural integrity of the epithelium.

Keywords: adherence junction; barrier; transient receptor potential vanilloid subtype 4; urinary bladder; urothelium.

MeSH terms

  • Animals
  • Blood-Nerve Barrier / physiology*
  • Blood-Nerve Barrier / ultrastructure
  • Humans
  • Immunohistochemistry
  • Intercellular Junctions / physiology*
  • Intercellular Junctions / ultrastructure
  • Kidney / physiology
  • Kidney / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • TRPV Cation Channels / metabolism
  • TRPV Cation Channels / physiology*
  • Urinary Bladder / physiology
  • Urinary Bladder / ultrastructure
  • Urogenital System / metabolism*
  • Urogenital System / ultrastructure
  • Urothelium / physiology
  • Urothelium / ultrastructure

Substances

  • TRPV Cation Channels
  • TRPV4 protein, human
  • Trpv4 protein, mouse