Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism
Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism
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DOI：
10.1172/jci200419081
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发表时间：
2004-02-01
影响因子：
15.9
通讯作者：
Yamashita, T
中科院分区：
文献类型：
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作者：
Shimada, T;Kakitani, M;Yamashita, T
无机磷酸盐对于 ECM 矿化至关重要，也是细胞代谢中重要分子的组成部分。对几种低磷血症疾病的研究表明，激素样分子可能调节血清磷酸盐浓度。 FGF23 最近被认为在几种低磷血症疾病中发挥重要的病理生理作用。我们在此通过生成 FGF23 缺失小鼠提供证据，证明 FGF23 是血清磷酸盐和 1,25-二羟基维生素 D (1,25[OH](2)D) 的生理调节剂。 Fgf23基因的破坏不会导致胚胎死亡，尽管纯合子小鼠表现出严重的生长迟缓、骨表型异常和明显缩短的寿命。 Fgf23(-/-)小鼠表现出显着高的血清磷酸盐，并且肾脏磷酸盐重吸收增加。他们还显示血清 1,25(OH)(2)D 升高，这是由于从 10 日龄起肾脏 25-羟基维生素 D-1α-羟化酶 (1α-OHase) 的表达增强。这些表型无法用目前已知的矿物质稳态调节因子来解释，表明 FGF23 对于正常的磷酸盐和维生素 D 代谢至关重要。
Inorganic phosphate is essential for ECM mineralization and also as a constituent of important molecules in cellular metabolism. Investigations of several hypophosphatemic diseases indicated that a hormone-like molecule probably regulates serum phosphate concentration. FGF23 has recently been recognized as playing important pathophysiological roles in several hypophosphatemic diseases. We present here the evidence that FGF23 is a physiological regulator of serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH](2)D) by generating FGF23-null mice. Disruption of the Fgf23 gene did not result in embryonic lethality, although homozygous mice showed severe growth retardation with abnormal bone phenotype and markedly short life span. The Fgf23(-/-) mice displayed significantly high serum phosphate with increased renal phosphate reabsorption. They also showed an elevation in serum 1,25(OH)(2)D that was due to the enhanced expression of renal 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase) from 10 days of age. These phenotypes could not be explained by currently known regulators of mineral homeostasis, indicating that FGF23 is essential for normal phosphate and vitamin D metabolism.