Research on regulatory mechanisms and their derangements of calcium and phosphate metabolism

血钙和血磷水平维持在很小的范围内。其中，甲状旁腺激素等钙调节激素在调节血钙水平中起着关键作用。甲状旁腺钙敏感受体是一种G蛋白偶联受体，调节甲状旁腺激素的分泌。我们通过研究几种由钙敏感受体基因突变引起的疾病，证明了这种钙敏感受体在调节血清钙水平中的重要性。另一方面，成纤维细胞生长因子23是一种体液因子，被认为是几种低磷血症的致病因素。我们已经证明，FGF23通过抑制肾小管对磷酸盐的重吸收而导致低磷血症，在生理磷酸盐代谢中发挥重要作用，并导致多种低磷血症性疾病。此外，通过建立FGF23检测系统，我们发现检测血清FGF23对低血磷症患者的诊断和随访有一定的参考价值。此外，FGF23基因的突变损害了FGF23的作用，被证明会导致高磷血症。这些结果表明FGF23在磷酸盐和骨代谢中的重要性。进一步研究FGF23的作用机制和对其产生的调控可能会为治疗骨骼和矿物质代谢紊乱提供新的治疗方法。

Serum calcium and phosphate levels are maintained within narrow ranges. Of these, calcium-regulating hormones like parathyroid hormone play pivotal roles in the regulation of serum calcium level. Calcium-sensing receptor in parathyroid gland is a G protein-coupled receptor that regulates parathyroid hormone secretion. We have demonstrated the importance of this calcium-sensing receptor in the regulation of serum calcium level by investigating several diseases caused by mutations in calcium-sensing receptor gene. On the other hand, fibroblast growth factor (FGF)23 is a humoral factor identified as a responsible factor for several hypophosphatemic diseases. We have demonstrated that FGF23 induces hypophosphatemia by suppressing renal tubular phosphate reabsorption and plays important roles in physiological phosphate metabolism as well as causes several hypophosphatemic diseases. In addition, by developing assay system for FGF23, We have shown that measurement of serum FGF23 is useful for the diagnosis and following hypophosphatemic patients. Furthermore, mutations in FGF23 gene that impair FGF23 action were shown to cause hyperphosphatemic disease. These results indicate the importance of FGF23 in phosphate and bone metabolism. Further research investigating the mechanism of action and regulation of production of FGF23 may lead to new therapeutic methods for derangements in bone and mineral metabolism.