Gene structure and regulation of the murine epithelial calcium channels ECaC1 and 2.
Gene structure and regulation of the murine epithelial calcium channels ECaC1 and 2.
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DOI：
10.1006/bbrc.2001.6121
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发表时间：
2001-12
影响因子：
3.1
通讯作者：
K. Weber;Reinhold G. Erben;Andreas Rump;Jerzy Adamski
中科院分区：
文献类型：
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作者：
K. Weber;Reinhold G. Erben;Andreas Rump;Jerzy Adamski
最近发现的上皮钙通道ECaC1和ECaC2被认为在肠道和肾脏的活性钙吸收中起重要作用。在人ECaC1的启动子序列中检测到维生素D响应元件（VDRE），并假设了类固醇激素1,25-二羟基维生素D(3) (1,25-(OH)（2)D(3)）对ECaC1的调节。在这项研究中，我们描述了两个小鼠ECaCs基因的结构，每个基因由定位在6号染色体上的15个外显子组成。小鼠ECaC2表达于125 -(OH)(2)D(3)的许多靶组织中，包括皮肤和成骨细胞，而ECaC1表达仅限于肾脏。通过筛选小鼠启动子序列，我们在ECaC1中检测到一个推测的VDRE，在ECaC2中检测到一个雌激素反应元件。然而，在具有突变的、无功能的维生素D受体的小鼠中进行的实验表明，肾脏中ECaC1和十二指肠中ECaC2的表达受钙水平的调节，而不受125 -(OH)(2)D(3)的调节。此外，与对照组小鼠相比，雌激素缺乏的卵巢切除（OVX）小鼠和补充雌二醇的OVX小鼠十二指肠ECaC2表达没有变化。我们得出结论，ECaC在肾脏和肠道中的表达受细胞外钙的调节，而不受维生素D或雌激素的调节。
The recently discovered epithelial calcium channels ECaC1 and ECaC2 are thought to play an important role in active calcium absorption in the intestine and kidney. Vitamin D-responsive elements (VDRE) were detected in the promoter sequence of human ECaC1 and regulation of ECaC by the steroid hormone 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) has been postulated. In this study we describe the structure of two murine ECaCs genes, each consisting of 15 exons localized on chromosome 6. Murine ECaC2 expression was found in many target tissues of 1,25-(OH)(2)D(3), including skin and osteoblastic cells, while ECaC1 expression is confined to the kidney. By screening the murine promoter sequences, we detected a putative VDRE in ECaC1 and an estrogen response element in ECaC2. However, experiments in mice with a mutant, nonfunctioning vitamin D receptor showed that expression of ECaC1 in the kidney and of ECaC2 in duodenum is regulated by calcium levels, but not by 1,25-(OH)(2)D(3). Also, estrogen-deficient ovariectomized (OVX) mice and OVX mice supplemented with estradiol showed unchanged duodenal ECaC2 expression compared with control mice. We conclude that ECaC expression in the kidney and the intestine is regulated by extracellular calcium but not by vitamin D or estrogen in vivo in mice.