Although vitamin D is critical for the function of the intestine, most studies have focused on the duodenum. We show that transgenic expression of the vitamin D receptor (VDR) only in the distal intestine of VDR null mice (KO/TG mice) results in the normalization of serum calcium and rescue of rickets. Although it had been suggested that calcium transport in the distal intestine involves a paracellular process, we found that the 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃]-activated genes in the proximal intestine associated with active calcium transport (Trpv6, S100g, and Atp2b1) are also induced by 1,25(OH)₂D₃ in the distal intestine of KO/TG mice. In addition, Slc30a10, encoding a manganese efflux transporter, was one of the genes most induced by 1,25(OH)₂D₃ in both proximal and distal intestine. Both villus and crypt were found to express Vdr and VDR target genes. RNA sequence (RNA-seq) analysis of human enteroids indicated that the effects of 1,25(OH)₂D₃ observed in mice are conserved in humans. Using Slc30a10^−/− mice, a loss of cortical bone and a marked decrease in S100g and Trpv6 in the intestine was observed. Our findings suggest an interrelationship between vitamin D and intestinal Mn efflux and indicate the importance of distal intestinal segments to vitamin D action.

中文翻译：

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1,25-二羟基维生素 D3 基因组作用分析揭示了小鼠小肠和人肠类中的钙调节和钙非依赖性效应


尽管维生素 D 对肠道功能至关重要，但大多数研究都集中在十二指肠。我们发现，维生素 D 受体 (VDR) 的转基因表达仅在 VDR 缺失小鼠（KO/TG 小鼠）的远端肠道中导致血清钙正常化并挽救佝偻病。尽管有人认为远端肠中的钙转运涉及细胞旁过程，但我们发现近端肠中的 1,25-二羟基维生素 D ₃ [1,25(OH) ₂ D ₃ ] 激活基因与活性钙相关。 KO/TG 小鼠远端肠中的转运（ Trpv6 、 S100g和Atp2b1 ）也由 1,25(OH) ₂ D ₃诱导。此外，编码锰外排转运蛋白的Slc30a10是近端和远端肠中最受1,25(OH) ₂ D ₃诱导的基因之一。发现绒毛和隐窝均表达Vdr和 VDR 靶基因。人肠类的 RNA 序列 (RNA-seq) 分析表明，在小鼠中观察到的 1,25(OH) ₂ D ₃的作用在人类中是保守的。使用Slc30a10 ^−/−小鼠，观察到皮质骨损失以及肠道中S100g和Trpv6显着减少。我们的研究结果表明维生素 D 和肠道锰流出之间存在相互关系，并表明远端肠段对维生素 D 作用的重要性。