The parathyroid is a target organ for FGF23 in rats
The parathyroid is a target organ for FGF23 in rats
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DOI：
10.1172/jci32409
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发表时间：
2007-12-01
影响因子：
15.9
通讯作者：
Silver, Justin
中科院分区：
文献类型：
--
作者：
Ben-Dov, Iddo Z.;Galitzer, Hillel;Silver, Justin
磷酸盐的体内平衡是通过肾脏外排和肠道和骨骼内流之间的平衡来维持的。FGF23是一种骨源性磷激素，作用于肾脏，增加磷酸盐排泄，抑制维生素d的生物合成。FGF23信号通过与跨膜蛋白Klotho作为辅助受体结合的几种FGF受体（fgfr）发挥最高功效。由于大多数组织表达FGFR， Klotho的表达决定了FGF23的靶器官。在这里，我们确定大鼠甲状旁腺是FGF23的靶器官。我们发现甲状旁腺表达Klotho和2个fgfr。重组FGF23导致甲状旁腺Klotho水平升高。此外，FGF23通过ERK1/2磷酸化激活甲状旁腺的MAPK通路，提高早期生长应答1 mRNA水平。通过大鼠和体外大鼠甲状旁腺培养，我们发现FGF23抑制甲状旁腺激素（PTH）分泌和PTH基因表达。fgf23诱导的PTH分泌减少被MAPK抑制剂阻止。这些数据表明，FGF23通过MAPK途径直接作用于甲状旁腺，降低血清PTH。这种骨-甲状旁腺内分泌轴增加了一个新的维度，以了解矿物质稳态。
Phosphate homeostasis is maintained by a counterbalance between efflux from the kidney and influx from intestine and bone. FGF23 is a bone-derived phosphaturic hormone that acts on the kidney to increase phosphate excretion and suppress biosynthesis of vitamin D. FGF23 signals with highest efficacy through several FGF receptors (FGFRs) bound by the transmembrane protein Klotho as a coreceptor. Since most tissues express FGFR, expression of Klotho determines FGF23 target organs. Here we identify the parathyroid as a target organ for FGF23 in rats. We show that the parathyroid gland expressed Klotho and 2 FGFRs. The administration of recombinant FGF23 led to an increase in parathyroid Klotho levels. In addition, FGF23 activated the MAPK pathway in the parathyroid through ERK1/2 phosphorylation and increased early growth response 1 mRNA levels. Using both rats and in vitro rat parathyroid cultures, we show that FGF23 suppressed both parathyroid hormone (PTH) secretion and PTH gene expression. The FGF23-induced decrease in PTH secretion was prevented by a MAPK inhibitor. These data indicate that FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH. This bone-parathyroid endocrine axis adds a new dimension to the understanding of mineral homeostasis.