Role of the vitamin D receptor in FGF23 action on phosphate metabolism
Role of the vitamin D receptor in FGF23 action on phosphate metabolism
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DOI：
10.1042/bj20041799
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发表时间：
2005-08-15
影响因子：
4.1
通讯作者：
Miyamoto, K
中科院分区：
文献类型：
--
作者：
Inoue, Y;Segawa, H;Miyamoto, K
FGF 23（fibroblast growth factor 23）是一种新型的磷酸化尿因子，其影响维生素D代谢和P-i的肾重吸收。本研究的目的是使用VDR（-/-）（VDR无效）小鼠表征VDR（维生素D受体）在FGF 23作用中的作用。将FGF 23 M（编码人FGF 23的R179 Q突变体的裸DNA）注射到VDR（-/-）和野生型VDR（+/+）小鼠中导致血清FGF 23水平升高，但对血清钙或甲状旁腺激素水平没有影响。相比之下，当与注射模拟载体或FGFWT（编码野生型人FGF 23的裸DNA）的对照相比时，注射FGF 23 M导致两组中血清Pi水平、肾Na/Pi共转运活性和II型转运蛋白水平显著降低。注射FGF 23 M导致VDR（-/-）和VDR（+/+）小鼠中25-羟基维生素D 1 α-羟化酶mRNA水平降低，而与模拟载体对照或FGF 23 WT处理的动物相比，FGF 23 M处理的动物中25-羟基维生素D 24-羟化酶mRNA水平显著增加。FGF 23 M对24-羟化酶的诱导程度取决于VDR，因为FGF 23 M显著降低了VDR（+/+）小鼠的血清1，25（OH）（2）D-3 [1，25-羟基维生素D-3]水平，但在VDR（-/-）小鼠中不显著。我们得出结论，FGF 23通过独立于VDR的机制降低肾β-i转运和25-羟基维生素D1 α-羟化酶水平。相反，25-羟基维生素D 24-羟化酶的诱导和FGF 23诱导的血清1，25（OH）（2）D-3水平的降低依赖于VDR。
FGF23 (fibroblast growth factor 23) is a novel phosphaturic factor that influences vitamin D metabolism and renal re-absorption of P-i. The goal of the present study was to characterize the role of the VDR (vitamin D receptor) in FGF23 action using VDR(-/-) (VDR null) mice. Injection of FGF23M (naked DNA encoding the R179Q mutant of human FGF23) into VDR(-/-) and wildtype VDR(+/+) mice resulted in an elevation in serum FGF23 levels, but had no effect on serum calcium or parathyroid hormone levels. In contrast, injection of FGF23M resulted in significant decreases in serum P-i levels, renal Na/P-i co-transport activity and type II transporter protein levels in both groups when compared with controls injected with mock vector or with FGFWT (naked DNA encoding wild-type human FGF23). Injection of FGF23M resulted in a decrease in 25-hydroxyvitamin D 1 alpha-hydroxylase mRNA levels in VDR(-/-) and VDR(+/+) mice, while 25-hydroxyvitamin D 24-hydroxylase mRNA levels were significantly increased in FGF23M-treated animals compared with mock vector control- or FGF23WT-treated animals. The degree of 24-hydroxylase induction by FGF23M was dependent on the VDR, since FGF23M significantly reduced the levels of serum 1,25(OH)(2)D-3 [1,25-hydroxyvitamin D-3] in VDR(+/+) mice, but not in VDR(-/-) mice. We conclude that FGF23 reduces renal P-i transport and 25-hydroxyvitamin D 1 alpha-hydroxylase levels by a mechanism that is independent of the VDR. In contrast, the induction of 25-hydroxyvitamin D 24-hydroxylase and the reduction of serum 1,25(OH)(2)D-3 levels induced by FGF23 are dependent on the VDR.