Physiological and pathological involvement of FGF-23 in mineral metabolism in human

1)FGF-23基因突变与肿瘤性钙质沉着症的关系我们在家族性肿瘤性钙质沉着症患者中发现FGF-23基因突变。突变后的FGF-23基因在哺乳动物细胞中表达后，FGF-23蛋白质明显降解，培养基中基本上没有全长的活性FGF-23。尽管FGF-23的降解产物在循环血液中积累，但在我们评估的肿瘤性钙质沉着患者中几乎检测不到全长FGF-23的血清水平。这些数据表明，人FGF-23功能的丧失导致肿瘤性钙质沉着，其表现为高磷酸盐血症和高血清1，25-二羟维生素D水平。2）循环FGF-23对健康志愿者血清磷酸盐水平急性升高的反应当静脉输注磷酸氢二钾使血清磷酸盐水平升高至6.0 mg/dl时，FGF-23的循环水平在实验的6小时内没有显著变化。该结果表明，与PTH分泌响应于高钙血症而迅速减少相反，FGF-23的分泌不能响应于血清磷酸盐水平的急性变化。血清FGF-23水平调节的生理机制有待进一步研究。3）肢端肥大症患者垂体手术前后血清磷酸盐和FGF-23水平肢端肥大症患者血清磷酸盐水平较高，手术成功后正常下降。当分析连续17例肢端肥大症患者的临床实验室数据时，血清FGF-23水平也伴随垂体手术而降低。这表明FGF-23的分泌会迅速响应人体血清磷酸盐水平的下降。

1) Mutation of FGF-23 gene involved in tumoral calcinosisWe identified mutation of FGF-23 gene in patients with familial tumoral calcinosis. Missense mutation was found. Expression the mutated FGF-23 gene in mammalian cells resulted in remarkable degradation of FGF-23 protein with essentially no full-length and active FGF-23 in culture media. Serum level of full-length FGF-23 was almost undetectable in patients with tumoral calcinossis we evaluated, although degradation products of FGF-23 were accumulated in circulating blood. These data indicate that loss of function of FGF-23 in human causes tumoral calcinosis that presents hyperphosphatemia and high serum level of 1,25-dihydroxyvitamin D.2) Response of circulating FGF-23 to acute increase in serum phosphate level in healthy volunteersWhen serum phosphate level was increased with intravenous infusion of dibasic potassium phosphate to 6.0 mg/dl, circulating level of FGF-23 did not change significantly within 6 hours of experiments. This result suggests that in contrast to rapid decrease in PTH secretion in response to hypercalcemia, secretion of FGF-23 cannot respond to acute changes of serum phosphate level. Physiological mechanisms for regulation of serum FGF-23 level are to be explored with further studies.3) Serum phosphate and FGF-23 levels in patients with acromegaly before and after pituitary surgerySerum phosphate level is higher in patients with acromegaly and decreases normally after successful surgery. When clinical laboratory data of consecutive 17 patients with acromegaly were analyzed, serum level of FGF-23 also concomitantly decreased with pituitary surgery. This indicates secretion of FGF-23 promptly responds to the decrease in serum phosphate level in human.