Renal claudin-14 expression is not required for regulating Mg 2+ balance in mice

Patrícia G Ferreira, Wouter H van Megen, Rebecca Siu Ga Tan, Christy H L Lee, Per Svenningsen, R Todd Alexander, Henrik Dimke*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


The kidneys play a crucial role in maintaining Ca 2+ and Mg 2+ homeostasis by regulating these minerals' reabsorption. In the thick ascending limb of Henle's loop (TAL), Ca 2+ and Mg 2+ are reabsorbed through the tight junctions by a shared paracellular pathway formed by claudin-16 and claudin-19. Hypercalcemia activates the Ca 2+-sensing receptor (CaSR) in the TAL, causing upregulation of pore-blocking claudin-14 (CLDN14), which reduces Ca 2+ and Mg 2+ reabsorption from this segment. In addition, a high-Mg 2+ diet is known to increase both urinary Mg 2+ and Ca 2+ excretion. Since Mg 2+ may also activate CaSR, we aimed to investigate whether CaSR-dependent increases in CLDN14 expression also regulate urinary Mg 2+ excretion in response to hypermagnesemia. Here, we show that a Mg 2+-enriched diet increased urinary Mg 2+ and Ca 2+ excretion in mice; however, this occurred without detectable changes in renal CLDN14 expression. The administration of a high-Mg 2+ diet to Cldn14 -/- mice did not cause more pronounced hypermagnesemia or significantly alter urinary Mg 2+ excretion. Finally, in vitro evaluation of CaSR-driven Cldn14 promoter activity in response to increasing Mg 2+ concentrations revealed that Cldn14 expression only increases at supraphysiological extracellular Mg 2+ levels. Together, these results suggest that CLDN14 is not involved in regulating extracellular Mg 2+ balance following high dietary Mg 2+ intake. NEW & NOTEWORTHY Using transgenic models and in vitro assays, this study examined the effect of Mg 2+ on regulating urinary excretion of Ca 2+ and Mg 2+ via activation of the Ca 2+-sensing receptor-claudin 14 (CLDN14) pathway. The study suggests that CLDN14 is unlikely to play a significant role in the compensatory response to hypermagnesemia.

TidsskriftAmerican journal of physiology. Renal physiology
Udgave nummer5
Sider (fra-til)F897-F907
StatusUdgivet - 3. maj 2021


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