The epithelial Mg2+ channel transient receptor potential melastatin 6 is regulated by dietary Mg2+ content and estrogens
The epithelial Mg2+ channel transient receptor potential melastatin 6 is regulated by dietary Mg2+ content and estrogens
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DOI：
10.1681/asn.2005070700
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发表时间：
2006-04-01
影响因子：
13.6
通讯作者：
Bindels, Rene J.
中科院分区：
文献类型：
--
作者：
Groenestege, Wouter M. Tiel;Hoenderop, Joost G.;Bindels, Rene J.
肾脏是负责调节体内Mg2+平衡的主要器官。最近对低镁血症伴继发性低钙血症的基因缺陷的鉴定阐明了瞬时受体电位melastatin 6 (TRPM6)作为跨上皮Mg2+转运的看门人，而其同源物TRPM7则与细胞Mg2+稳态有关。本研究的目的是确定小鼠体内的组织分布以及膳食 Mg2+ 和激素对 TRPM6 和 TRPM7 的调节。这项研究表明，TRPM6 主要在肾脏、肺、盲肠和结肠中表达，而 TRPM7 则分布广泛。小鼠饮食中 Mg2+ 限制导致低镁血症和肾脏 Mg2+ 和 Ca2+ 保存，而富含 Mg2+ 的饮食则导致尿 Mg2+ 和 Ca2+ 排泄增加。相反，限制 Mg2+ 显着上调肾脏 TRPM6 mRNA 水平，而富含 Mg2+ 的饮食则增加结肠中 TRPM6 mRNA 的表达。膳食 Mg2+ 不会改变小鼠肾脏和结肠中 TRPM7 mRNA 的表达。此外，研究还表明，17β-雌二醇而非 1,25-二羟基维生素 D-3 或甲状旁腺激素可调节 TRPM6 肾 mRNA 水平。在这些条件下，肾 TRPM7 mRNA 丰度保持不变。卵巢切除大鼠的肾TRPM6 mRNA水平显着降低，而17β-雌二醇治疗使TRPM6 mRNA水平正常化。总之，肾脏、肺、盲肠和结肠可能构成小鼠活性 Mg2+（再）吸收的主要部位。此外，Mg2+限制和17β-雌二醇上调肾脏TRPM6 mRNA水平，而富含Mg2+的饮食刺激结肠中TRPM6 mRNA表达，支持TRPM6在跨上皮Mg2+转运中的看门人功能。
The kidney is the principal organ responsible for the regulation of the body Mg2+ balance. Identification of the gene defect in hypomagnesemia with secondary hypocalcemia recently elucidated transient receptor potential melastatin 6 (TRPM6) as the gatekeeper in transepithelial Mg2+ transport, whereas its homolog, TRPM7, is implicated in cellular Mg2+ homeostasis. The aim of this study was to determine the tissue distribution in mouse and regulation of TRPM6 and TRPM7 by dietary Mg2+ and hormones. This study demonstrates that TRPM6 is expressed predominantly in kidney, lung, cecum, and colon, whereas TRPM7 is distributed ubiquitously. Dietary Mg2+ restriction in mice resulted in hypomagnesemia and renal Mg2+ and Ca2+ conservation, whereas a Mg2+-enriched diet led to increased urinary Mg2+ and Ca2+ excretion. Conversely, Mg2+ restriction significantly upregulated renal TRPM6 mRNA levels, whereas a Mg2+ enriched diet increased TRPM6 mRNA expression in colon. Dietary Mg2+ did not alter TRPM7 mRNA expression in mouse kidney and colon. In addition, it was demonstrated that 17 beta-estradiol but not 1,25-dihydroxyvitamin D-3 or parathyroid hormone regulates TRPM6 renal mRNA levels. Renal TRPM7 mRNA abundance remained unaltered under these conditions. The renal TRPM6 mRNA level in ovariectomized rats was significantly reduced, whereas 17 beta-estradiol treatment normalized TRPM6 mRNA levels. In conclusion, kidney, lung, cecum, and colon likely constitute the main sites of active Mg2+ (re)absorption in the mouse. In addition, Mg2+ restriction and 17 beta-estradiol upregulated renal TRPM6 mRNA levels, whereas a Mg2+-enriched diet stimulated TRPM6 mRNA expression in colon, supporting the gatekeeper function of TRPM6 in transepithelial Mg2+ transport.