Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 320, Issue 5, Pages F897-F907Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00590.2020
Keywords
Ca2+-sensing receptor; claudin-14; kidney; magnesium; tight junctions
Categories
Funding
- Canadian Institutes of Health Research
- Fabrikant Vilhelm Pedersen og Hustrus Mindelegat
- Novo Nordisk Foundation
- Beckett Foundation
- Carlsberg Foundation
- Independent Research Fund Denmark
- Erasmusthorn [2018/Ethorn/4458087]
Ask authors/readers for more resources
This study investigated the role of Mg2+ in regulating urinary excretion of Ca2+ and Mg2+ through the Ca2+-sensing receptor-claudin 14 (CLDN14) pathway using transgenic models and in vitro assays. The results suggest that CLDN14 is unlikely to play a significant role in the compensatory response to hypermagnesemia.
The kidneys play a crucial role in maintaining Ca2+ and Mg2+ homeostasis by regulating these minerals' reabsorption. In the thick ascending limb of Henle's loop (TAL), Ca2+ and Mg2+ are reabsorbed through the tight junctions by a shared paracellular pathway formed by claudin-16 and claudin-19. Hypercalcemia activates the Ca2+-sensing receptor (CaSR) in the TAL, causing upregulation of pore-blocking claudin-14 (CLDN14), which reduces Ca2+ and Mg2+ reabsorption from this segment. In addition, a high-Mg2+ diet is known to increase both urinary Mg2+ and Ca2+ excretion. Since Mg2+ may also activate CaSR, we aimed to investigate whether CaSR-dependent increases in CLDN14 expression also regulate urinary Mg2+ excretion in response to hypermagnesemia. Here, we show that a Mg2+-enriched diet increased urinary Mg2+ and Ca2+ excretion in mice; however, this occurred without detectable changes in renal CLDN14 expression. The administration of a high-Mg2+ diet to Cldn14(-/-) mice did not cause more pronounced hypermagnesemia or significantly alter urinary Mg2+ excretion. Finally, in vitro evaluation of CaSR-driven Cldn14 promoter activity in response to increasing Mg2+ concentrations revealed that Cldn14 expression only increases at supraphysiological extracellular Mg2+ levels. Together, these results suggest that CLDN14 is not involved in regulating extracellular Mg2+ balance following high dietary Mg2+ intake. NEW & NOTEWORTHY Using transgenic models and in vitro assays, this study examined the effect of Mg2+ on regulating urinary excretion of Ca2+ and Mg2+ via activation of the Ca2+-sensing receptor-claudin 14 (CLDN14) pathway. The study suggests that CLDN14 is unlikely to play a significant role in the compensatory response to hypermagnesemia.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available