How do we sense phosphate to regulate serum phosphate level?
How do we sense phosphate to regulate serum phosphate level?
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我们如何感知磷酸盐来调节血清磷酸盐水平？
DOI：
10.1007/s00774-019-01066-0
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发表时间：
2020
影响因子：
3.3
通讯作者：
Toshio Matsumoto
中科院分区：
文献类型：
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作者：
Seiji Fukumoto;Yuichi Takashi;Maria Tsoumpra;Shun Sawatsubashi;Toshio Matsumoto
磷酸盐水平异常可导致佝偻病/骨软化症和异位钙化等多种病理情况，这表明一定存在一个在狭窄范围内调节磷酸盐水平的系统。FGF23已被证明是调节血清磷酸盐水平的重要激素。FGF23结合kloho - fgf受体复合物降低血清磷酸盐水平。一些报道表明，FGF受体参与FGF23产生的调控。也有研究表明，高的细胞外磷酸盐可以激活几种细胞内信号通路。然而，目前尚不清楚磷酸盐是否以及如何调节体内FGF23的产生。我们最近的研究结果表明，高细胞外磷酸盐直接激活FGF受体1，下游细胞内信号传导增强FGF23的产生。因此，存在一个涉及FGF受体和FGF23的调节血清磷酸盐水平的负反馈系统。我们认为FGF受体至少是维持血清磷酸盐水平的磷酸盐传感器之一。
Abnormal phosphate levels result in several pathological conditions such as rickets/osteomalacia and ectopic calcification indicating that there must be a system that regulates phosphate level within a narrow range. FGF23 has been shown to be an essential hormone regulating serum phosphate level. FGF23 binds to Klotho-FGF receptor complex to reduce serum phosphate level. Several reports suggested that FGF receptor is involved in the regulation of FGF23 production. It has been also shown that high extracellular phosphate can activate several intracellular signaling pathways. However, it has been unclear whether and how phosphate regulates FGF23 production in vivo. Our recent results indicate that high extracellular phosphate directly activates FGF receptor 1 and the downstream intracellular signaling enhances FGF23 production. Thus, there is a negative feedback system for the regulation of serum phosphate level involving FGF receptor and FGF23. We propose that FGF receptor works at least as one of phosphate sensors in the maintenance of serum phosphate level.