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1α,25-二羟维生素D3对小鼠肠道和肾脏中上皮钙通道基因表达的调控

Regulation of gene expression of epithelial calcium channels in intestine and kidney of mice by 1alpha,25-dihydroxyvitamin D3.

作者信息

Okano Toshio, Tsugawa Naoko, Morishita Atsushi, Kato Shigeaki

机构信息

Department of Hygienic Sciences, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.

出版信息

J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):335-8. doi: 10.1016/j.jsbmb.2004.03.024.

DOI:10.1016/j.jsbmb.2004.03.024
PMID:15225796
Abstract

In wild-type (VDR(+/+)) mice, ECaC2 expression was confirmed in the intestine and kidney, while ECaC1 expression was exclusively confined to the kidney. Both mRNAs expression of ECaC1 and ECaC2 in the kidney and ECaC2 mRNA expression in the intestine increased time- and dose-dependently in response to 1alpha,25(OH)(2)D(3) injection in VDR(+/+) mice, but not in VDR(-/-) mice. The mRNA levels of ECaC2 in the intestine of VDR(-/-) mice were remarkably reduced when compared to VDR(+/+) mice, while no significant differences were observed in both mRNA levels of ECaC1 and ECaC2 in the kidney between VDR(+/+) mice and VDR(-/-) mice. In the primary renal tubular cells (PRTC) isolated from VDR(+/+) mice, both ECaCs mRNA expression increased in response to 1alpha,25(OH)(2)D(3) treatment, but not in the PRTC of VDR(-/-) mice. PTH increased both ECaCs mRNA expression in the PRTC of VDR(+/+) mice. These results suggest that 1alpha,25(OH)(2)D(3) directly modulates the gene expression of ECaC1 and ECaC2 together with PTH in the kidney of mice. 1alpha,25(OH)(2)D(3) also modulates the gene expression of ECaC2 in the intestine of mice, however, further studies are needed to elucidate the direct action of 1alpha,25(OH)(2)D(3) on the expression of ECaC2 in the intestine.

摘要

在野生型(VDR(+/+))小鼠中,肠和肾中均证实有ECaC2表达,而ECaC1表达仅局限于肾。VDR(+/+)小鼠注射1α,25(OH)₂D₃后,肾中ECaC1和ECaC2的mRNA表达以及肠中ECaC2的mRNA表达均呈时间和剂量依赖性增加,但VDR(-/-)小鼠则不然。与VDR(+/+)小鼠相比,VDR(-/-)小鼠肠中ECaC2的mRNA水平显著降低,而VDR(+/+)小鼠和VDR(-/-)小鼠肾中ECaC1和ECaC2的mRNA水平均未观察到显著差异。在从VDR(+/+)小鼠分离的原代肾小管细胞(PRTC)中,1α,25(OH)₂D₃处理后ECaCs的mRNA表达均增加,但VDR(-/-)小鼠的PRTC中则无此现象。甲状旁腺激素(PTH)使VDR(+/+)小鼠PRTC中ECaCs的mRNA表达均增加。这些结果表明,1α,25(OH)₂D₃在小鼠肾中与PTH一起直接调节ECaC1和ECaC2的基因表达。1α,25(OH)₂D₃还调节小鼠肠中ECaC2的基因表达,然而,需要进一步研究以阐明1α,25(OH)₂D₃对肠中ECaC2表达的直接作用。

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