Renal claudin-14 expression is not required for regulating Mg(2+) balance in mice.
SourceAmerican Journal of Physiology : Renal Physiology, 320, 5, (2021), pp. F897-F907
Article / Letter to editor
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American Journal of Physiology : Renal Physiology
SubjectRadboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences
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.
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