Wood R J, Tchack L, Taparia S
Mineral Bioavailability Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
BMC Physiol. 2001;1:11. doi: 10.1186/1472-6793-1-11. Epub 2001 Aug 17.
The active hormonal form of vitamin D (1,25-dihydroxyvitamin D) is the primary regulator of intestinal calcium absorption efficiency. In vitamin D deficiency, intestinal calcium absorption is low leading to an increased risk of developing negative calcium balance and bone loss. 1,25-dihydroxyvitamin D has been shown to stimulate calcium absorption in experimental animals and in human subjects. However, the molecular details of calcium transport across the enterocyte are not fully defined. Recently, two novel epithelial calcium channels (CaT1/ECaC2 and ECaC1/CaT2) have been cloned and suggested to be important in regulating intestinal calcium absorption. However, to date neither gene has been shown to be regulated by vitamin D status. We have previously shown that 1,25-dihydroxyvitamin stimulates transcellular calcium transport in Caco-2 cells, a human intestinal cell line.
In the current study, we have demonstrated that Caco-2 cells express low but detectable levels of CaT1 mRNA in the absence of 1,25-dihydroxyvitamin D treatment. CaT1 mRNA expression is rapidly up regulated (4-fold increase at 4 h and 10-fold at 24 h) by treatment with 1,25-dihydroxyvitamin D (10(-7) moles/L). Moreover, the increase in CaT1 mRNA expression preceded by several hours the vitamin D induction of calbindin D9K, a putative cytosolic calcium transport protein.
These observations are the first to demonstrate regulation of CaT1 expression by vitamin D and are consistent with a new model of intestinal calcium absorption wherein vitamin D-mediated changes in brush border membrane CaT1 levels could be the primary gatekeeper regulating homeostatic modulation of intestinal calcium absorption efficiency.
维生素D的活性激素形式（1,25 - 二羟基维生素D）是肠道钙吸收效率的主要调节因子。在维生素D缺乏时，肠道钙吸收较低，导致出现负钙平衡和骨质流失的风险增加。1,25 - 二羟基维生素D已被证明可刺激实验动物和人类受试者的钙吸收。然而，钙跨肠上皮细胞转运的分子细节尚未完全明确。最近，两种新型上皮钙通道（CaT1/ECaC2和ECaC1/CaT2）已被克隆，并被认为在调节肠道钙吸收中起重要作用。然而，迄今为止，尚未发现这两个基因受维生素D状态的调节。我们之前已经表明，1,25 - 二羟基维生素可刺激人肠道细胞系Caco - 2细胞中的跨细胞钙转运。
在当前研究中，我们证明在未用1,25 - 二羟基维生素D处理的情况下，Caco - 2细胞表达低水平但可检测到的CaT1 mRNA。用1,25 - 二羟基维生素D（10^(-7)摩尔/升）处理后，CaT1 mRNA表达迅速上调（4小时时增加4倍，24小时时增加10倍）。此外，CaT1 mRNA表达的增加比维生素D诱导的钙结合蛋白D9K（一种假定的胞质钙转运蛋白）提前数小时。
这些观察结果首次证明了维生素D对CaT1表达的调节，并且与肠道钙吸收的新模型一致，其中维生素D介导的刷状缘膜CaT1水平变化可能是调节肠道钙吸收效率稳态调节的主要守门人。
