Institute of Physiology, University of Zürich, Zürich, Switzerland.
National Center of Competence in Research Kidney.CH, Zürich, Switzerland.
Acta Physiol (Oxf). 2022 Jun;235(2):e13815. doi: 10.1111/apha.13815. Epub 2022 Apr 6.
Dietary inorganic phosphate (Pi) modulates renal Pi reabsorption by regulating the expression of the NaPi-IIa and NaPi-IIc Pi transporters. Here, we aimed to clarify the role of several Pi-regulatory mechanisms including parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) and inositol hexakisphosphate kinases (IP6-kinases) in the acute regulation of NaPi-IIa and NaPi-IIc.
Wildtype (WT) and PTH-deficient mice (PTH-KO) with/without inhibition of FGF23 signalling were gavaged with Pi/saline and examined at 1, 4 and 12 h.
Pi-gavage elevated plasma Pi and decreased plasma Ca in both genotypes after 1 h Within 1 h, Pi-gavage decreased NaPi-IIa abundance in WT and PTH-KO mice. NaPi-IIc was downregulated 1 h post-administration in WT and after 4 h in PTH-KO. PTH increased after 1 h in WT animals. After 4 h Pi-gavage, FGF23 increased in both genotypes being higher in the KO group. PTHrp and dopamine were not altered by Pi-gavage. Blocking FGF23 signalling blunted PTH upregulation in WT mice and reduced NaPi-IIa downregulation in PTH-KO mice 4 h after Pi-gavage. Inhibition of IP6-kinases had no effect.
(1) Acute downregulation of renal Pi transporters in response to Pi intake occurs also in the absence of PTH and FGF23 signalling, (2) when FGF23 signalling is blocked, a partial contribution of PTH is revealed, (3) IP6 kinases, intracellular Pi-sensors in yeast and bacteria, are not involved, and (4) Acute Pi does not alter PTHrp and dopamine. Thus, signals other than PTH, PTHrp, FGF23 and dopamine contribute to renal adaption.
膳食无机磷（Pi）通过调节 NaPi-IIa 和 NaPi-IIc Pi 转运体的表达来调节肾脏 Pi 重吸收。在这里，我们旨在阐明包括甲状旁腺激素（PTH）、成纤维细胞生长因子 23（FGF23）和肌醇六磷酸激酶（IP6-kinases）在内的几种 Pi 调节机制在 NaPi-IIa 和 NaPi-IIc 的急性调节中的作用。
用 Pi/盐水灌胃野生型（WT）和甲状旁腺激素缺乏型（PTH-KO）小鼠，并在 1、4 和 12 小时进行检查。
Pi 灌胃后，1 小时内两种基因型的血浆 Pi 升高，血浆 Ca 降低。1 小时内，Pi 灌胃降低了 WT 和 PTH-KO 小鼠的 NaPi-IIa 丰度。WT 小鼠给药后 1 小时内下调了 NaPi-IIc，而 PTH-KO 小鼠则在 4 小时后下调。WT 动物在 1 小时后 PTH 增加。Pi 灌胃 4 小时后，两种基因型的 FGF23 均增加，KO 组更高。Pi 灌胃后 PTHrp 和多巴胺没有改变。阻断 FGF23 信号转导减弱了 WT 小鼠的 PTH 上调，并降低了 PTH-KO 小鼠在 Pi 灌胃 4 小时后的 NaPi-IIa 下调。抑制 IP6-kinases 没有影响。
（1）Pi 摄入后，肾脏 Pi 转运体的急性下调也发生在缺乏 PTH 和 FGF23 信号转导的情况下，（2）当阻断 FGF23 信号转导时，揭示了 PTH 的部分贡献，（3）IP6 激酶，酵母和细菌中的细胞内 Pi 传感器，不参与，（4）急性 Pi 不会改变 PTHrp 和多巴胺。因此，除了 PTH、PTHrp、FGF23 和多巴胺之外，其他信号参与了肾脏的适应。
