Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Nephrol Dial Transplant. 2013 Dec;28(12):2983-93. doi: 10.1093/ndt/gft358. Epub 2013 Oct 3.
Magnesium (Mg(2+)) is an essential electrolyte with important physiological functions. Consequently, hypomagnesaemia, an electrolyte disorder frequently diagnosed in critically ill patients, can have life-threatening consequences. The kidney plays a central role in the regulation of the Mg(2+) balance. The present study investigated the molecular consequences of dietary Mg(2+) restriction on renal Mg(2+) transporters.
Two groups of 10 mice were fed a Mg(2+)-deficient diet or a Mg(2+)-enriched diet for 2 weeks. Serum and urine electrolyte concentrations were assayed. Next, renal mRNA expression levels of Mg(2+)-related genes were measured to determine their sensitivity to the dietary Mg(2+) content. Subsequently, parvalbumin (PV) and the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), both co-expressed in the distal convoluted tubule (DCT) with TRPM6, were further analysed at the protein level using immunoblotting and immunohistochemistry.
Serum and urine electrolyte measurements revealed that dietary Mg(2+) restriction resulted in significant reduction of serum Mg(2+) and Ca(2+) levels, and that the urinary excretion of these ions was also markedly reduced, while phosphate (Pi) excretion was significantly increased. In addition, the serum FGF23 level was markedly increased, whereas Pi was not significantly changed in the Mg(2+)-restricted mouse group. The renal abundance of hepatocyte nuclear factor 1 homeobox B (HNF1B) and the epithelial Mg(2+) channel TRPM6 were increased in response to dietary Mg(2+) restriction, whereas other magnesiotropic transporters were not affected. PV abundance was upregulated, while NCC was significantly downregulated. Furthermore, the expression levels of the epithelial Ca(2+) channel TRPV5 and calbindin-D28K were markedly reduced in the low Mg(2+) group.
Our data indicate an essential adaptive role for DCT during hypomagnesaemia since TRPM6, HNF1B, PV and NCC expression levels were adjusted. Moreover, hypomagnesaemia resulted in severe changes in Ca(2+) and Pi reabsorption and expression levels of calciotropic proteins.
镁（Mg(2+)）是一种重要的电解质，具有重要的生理功能。因此，低镁血症是一种在危重病患者中经常诊断出的电解质紊乱，可能会有生命危险。肾脏在调节镁（Mg(2+)）平衡方面起着核心作用。本研究探讨了饮食镁（Mg(2+)）限制对肾脏镁（Mg(2+)）转运体的分子影响。
两组各 10 只小鼠分别喂食低镁（Mg(2+)）饮食或富含镁（Mg(2+)）的饮食 2 周。测定血清和尿液电解质浓度。然后，测量肾脏与镁（Mg(2+)）相关基因的 mRNA 表达水平，以确定其对饮食镁（Mg(2+)）含量的敏感性。随后，使用免疫印迹和免疫组织化学法进一步分析在远端曲管（DCT）与 TRPM6 共表达的副甲状腺蛋白（PV）和噻嗪敏感的 Na(+)-Cl(-)共转运蛋白（NCC）。
血清和尿液电解质测量表明，饮食镁（Mg(2+)）限制导致血清镁（Mg(2+)）和钙（Ca(2+)）水平显著降低，这些离子的尿排泄也明显减少，而磷酸盐（Pi）排泄显著增加。此外，血清 FGF23 水平显著增加，而镁（Mg(2+)）限制组的 Pi 没有明显变化。饮食镁（Mg(2+)）限制导致肝核因子 1 同源盒 B（HNF1B）和上皮镁（Mg(2+)）通道 TRPM6 的肾脏丰度增加，而其他镁转运体没有受到影响。PV 丰度上调，而 NCC 显著下调。此外，低镁（Mg(2+)）组上皮钙（Ca(2+)）通道 TRPV5 和钙结合蛋白 D28K 的表达水平明显降低。
我们的数据表明，在低镁血症期间 DCT 发挥了重要的适应性作用，因为 TRPM6、HNF1B、PV 和 NCC 的表达水平得到了调节。此外，低镁血症导致钙（Ca(2+)）和 Pi 重吸收严重变化和钙调节蛋白的表达水平降低。
