Aarhus University Seal / Aarhus Universitets segl

Localization and regulation of claudin-14 in experimental models of hypercalcemia

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Sebastian Frische
  • R. Todd Alexander, University of Alberta
  • ,
  • Patrícia Ferreira, Syddansk Universitet
  • ,
  • Rebecca Siu Ga Tan, University of Alberta
  • ,
  • Weidong Wang, Sun Yat-Sen University
  • ,
  • Per Svenningsen, Syddansk Universitet
  • ,
  • Karsten Skjødt, Syddansk Universitet
  • ,
  • Henrik Dimke, Syddansk Universitet, Odense Universitetshospital

Variations in the claudin-14 (CLDN14) gene have been linked to increased risk of hypercalciuria and kidney stone formation. However, the exact cellular localization of CLDN14 and its regulation remain to be fully delineated. To this end, we generated a novel antibody that allowed the detection of CLDN14 in paraffin-embedded renal sections. This showed CLDN14 to be detectable in the kidney only after induction of hypercalcemia in rodent models. Protein expression in the kidney is localized exclusively to the thick ascending limbs (TALs), mainly restricted to the cortical and upper medullary portion of the kidney. However, not all cells in the TALs expressed the tight junction protein. In fact, CLDN14 was primarily expressed in cells also expressing CLDN16 but devoid of CLDN10. CLDN14 appeared in very superficial apical cell domains and near cell junctions in a belt-like formation along the apical cell periphery. In transgenic mice, Cldn14 promotor-driven LacZ activity did not show complete colocalization with CLDN14 protein nor was it increased by hypercalcemia, suggesting that LacZ activity cannot be used as a marker for CLDN14 localization and regulation in this model. In conclusion, CLDN14 showed a restricted localization pattern in the apical domain of select cells of the TAL.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology - Renal Physiology
Vol/bind320
Nummer1
Sider (fra-til)F74-F86
Antal sider13
ISSN0363-6127
DOI
StatusUdgivet - jan. 2021

Se relationer på Aarhus Universitet Citationsformater

ID: 213938586