Aranami Fumito, Segawa Hiroko, Furutani Junya, Kuwahara Shoji, Tominaga Rieko, Hanabusa Etsuyo, Tatsumi Sawako, Kido Shinsuke, Ito Mikiko, Miyamoto Ken-ichi
Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
J Med Invest. 2010 Feb;57(1-2):95-108. doi: 10.2152/jmi.57.95.
Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axis 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 WT mice, plasma FGF23 concentration was significantly increased. Urinary Pi excretion levels were significantly higher in Cd-injected WT mice than in control group. Plasma Pi concentration decreased only slightly compared with control group. No change was observed in plasma parathyroid hormone and 1,25-dihydroxy vitamin D(3) in both group of mice. We observed a decrease in phosphate transport activity and also decrease in expression of renal phosphate transporter SLC34A3 [NaPi-IIc/NPT2c], but not SLC34A1 [NaPi-IIa/NPT2a]. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice which expresses Npt2c as a major NaPi co-transporter. Injecting Cd to Npt2aKO mice induced significant increase in plasma FGF23 concentration and urinary Pi excretion levels. Furthermore, we observed a decrease in phosphate transport activity and renal Npt2c expression in Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with the FGF23/klotho axis.
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）/α-klotho轴是骨-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。向野生型（WT）小鼠注射镉后，血浆FGF23浓度显著升高。注射镉的WT小鼠的尿磷排泄水平显著高于对照组。与对照组相比，血浆磷浓度仅略有下降。两组小鼠的血浆甲状旁腺激素和1,25-二羟基维生素D（3）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SLC34A3[NaPi-IIc/NPT2c]的表达也降低，但SLC34A1[NaPi-IIa/NPT2a]未降低。此外，我们研究了镉对以Npt2c作为主要NaPi共转运体的Npt2a基因敲除（KO）小鼠中Npt2c的影响。向Npt2a基因敲除小鼠注射镉会导致血浆FGF23浓度和尿磷排泄水平显著增加。此外，我们观察到注射镉的Npt2a基因敲除小鼠的磷酸盐转运活性和肾Npt2c表达降低。本研究表明，镉诱导的低磷血症可能与FGF23/α-klotho轴密切相关。
