Kido Shinsuke, Fujihara Marina, Nomura Kengo, Sasaki Shohei, Shiozaki Yuji, Segawa Hiroko, Tatsumi Sawako, Miyamoto Ken-ichi
Department of Molecular Nutrition, the University of Tokushima Graduate School, Tokushima, Japan.
Nihon Eiseigaku Zasshi. 2012;67(4):464-71. doi: 10.1265/jjh.67.464.
Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. Fibroblast growth factor 23 (FGF23) serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. Following Cd injection into C57BL/6J mice, plasma FGF23 concentration significantly increased. The urinary Pi excretion level was significantly higher in the Cd-injected C57BL/6J mice than in the control group. Plasma Pi concentration decreased only slightly in the Cd-injected mice compared with the control group. No changes were observed in the concentration of the plasma parathyroid hormone and 1,25-dihydroxy vitamin D(3) in both groups of mice. We observed a decrease in phosphate transport activity and also a decrease in the expression level of renal phosphate transporter Npt2c, but not that of Npt2a. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice, which expresses Npt2c as a major NaPi cotransporter. Injecting Cd to Npt2aKO mice induced a significant increase in plasma FGF23 concentration and urinary Pi excretion level. Furthermore, we observed decreases in phosphate transport activity and renal Npt2c expression level in the Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with FGF23.
在人类和实验动物中，镉（Cd）暴露后均有磷尿症的记录。成纤维细胞生长因子23（FGF23）是骨-肾轴中维持磷酸盐稳态的重要途径。在本研究中，我们调查了镉对小鼠磷酸盐（Pi）稳态的影响。向C57BL/6J小鼠注射镉后，血浆FGF23浓度显著升高。注射镉的C57BL/6J小鼠的尿Pi排泄水平显著高于对照组。与对照组相比，注射镉的小鼠血浆Pi浓度仅略有下降。两组小鼠血浆甲状旁腺激素和1,25-二羟基维生素D(3)的浓度均未观察到变化。我们观察到磷酸盐转运活性降低，肾磷酸盐转运体Npt2c的表达水平也降低，但Npt2a的表达水平未降低。此外，我们检查了镉对Npt2a基因敲除（KO）小鼠中Npt2c的影响，该小鼠将Npt2c作为主要的NaPi共转运体表达。向Npt2a KO小鼠注射镉会导致血浆FGF23浓度和尿Pi排泄水平显著增加。此外，我们观察到注射镉的Npt2a KO小鼠的磷酸盐转运活性和肾Npt2c表达水平降低。本研究表明，镉诱导的低磷血症可能与FGF23密切相关。
