Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells
Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells
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DOI：
10.1152/ajpendo.00502.2004
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发表时间：
2005-06-01
影响因子：
5.1
通讯作者：
Miyamoto, K
中科院分区：
文献类型：
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作者：
Ito, M;Sakai, Y;Miyamoto, K
成纤维细胞生长因子-23（FGF-23）在磷酸盐平衡和维生素D代谢中起重要的病理生理作用。为了阐明FGF-23的精确生理调节，我们表征了小鼠FGF-23 5 '侧翼区并分析了其启动子活性。小鼠FGF-23基因的5 '侧翼区含有TFIID位点（TATA盒）和几个推定的转录因子结合位点，包括MZF 1、加塔-1和c-Ets-1基序，但它不含有维生素D反应元件的典型序列。质粒酶编码554-bp（pGL/-0.6）、364-bp（pGL/-0.4）和200-bp（pGL/-0.13）启动子区，其含有TFIID元件和+1-bp片段，在转染测定中驱动荧光素酶报告基因的下游表达。我们还发现FGF-23 mRNA在K-562红白血病细胞系中表达，而在MC 3 T3-E1、Raji和Hep G2人癌细胞中不表达。在高磷酸盐存在下用1，25-二羟维生素D-3处理显著刺激pGL/-0.6活性，但钙没有影响。此外，血浆FGF-23水平受饮食和血浆无机磷酸盐浓度的影响。最后，维生素D受体缺失小鼠的血浆FGF-23水平显著低于野生型小鼠。本研究表明，维生素D和血浆磷酸盐水平是小鼠FGF-23基因转录的重要调节因子。
Fibroblast growth factor-23 (FGF-23) has been recently identified as playing an important pathophysiological role in phosphate homeostasis and vitamin D metabolism. To elucidate the precise physiological regulation of FGF-23, we characterized the mouse FGF-23 5'-flanking region and analyzed its promoter activity. The 5'-flanking region of the mouse FGF-23 gene contained a TFIID site ( TATA box) and several putative transcription factor binding sites, including MZF1, GATA-1 and c-Ets-1 motifs, but it did not contain the typical sequences of the vitamin D response element. Plasmids encoding 554-bp (pGL/-0.6), 364-bp (pGL/-0.4) and 200-bp (pGL/-0.13) promoter regions containing the TFIID element and +1-bp fragments drove the downstream expression of a luciferase reporter gene in transfection assays. We also found that FGF-23 mRNA was expressed in K-562 erythroleukemia cell lines but not in MC3T3-E1, Raji, or Hep G2 human carcinoma cells. Treatment with 1,25-dihydroxyvitamin D-3 in the presence of high phosphate markedly stimulated pGL/-0.6 activity, but calcium had no effect. In addition, the plasma FGF-23 levels were affected by the dietary and plasma inorganic phosphate concentrations. Finally, the levels of plasma FGF-23 in vitamin D receptor-null mice were significantly lower than in wild-type mice. The presents study demonstrated that vitamin D and the plasma phosphate level are important regulators of the transcription of the mouse FGF-23 gene.