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

FGF-23 在人体矿物质代谢中的生理和病理作用

基本信息

批准号：
17590972
负责人：
TAKEUCHI Yasuhiro
金额：
$ 2.11万
依托单位：
Okinaka Memorial Institute for Medical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590972/
关键词：
FGF-23 phosphate metabolism vitamin D metabolism tumoral calcinosis acromegaly

项目摘要

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.

1）参与肿瘤钙化的FGF-23基因的突变鉴定出家族性肿瘤钙化患者的FGF-23基因突变。发现错义突变。表达哺乳动物细胞中突变的FGF-23基因导致FGF-23蛋白的显着降解，在培养基中基本上没有全长和活性FGF-23。我们评估了肿瘤钙的患者的全长FGF-23的血清水平几乎无法检测到，尽管在循环血液中积累了FGF-23的降解产物。这些数据表明，FGF-23在人体中的功能丧失导致肿瘤钙化，钙化性钙化，高磷酸血症和高血清水平为1,25-二羟基毒素D.2）循环FGF-23对健康志愿者磷酸盐水平的血清磷酸盐水平的急性增加的循环FGF-23的反应。 MG/DL，FGF-23的循环水平在实验后6小时内没有显着变化。该结果表明，与响应高钙血症的PTH分泌快速降低相反，FGF-23的分泌无法应对血清磷酸盐水平的急性变化。通过进一步的研究，将探索用于调节血清FGF-23水平的生理机制。3）垂体手术磷酸盐磷酸盐症患者的血清磷酸血清和FGF-23水平较高，急诊症患者较高，并在成功手术后正常降低。当分析连续17例肢端肥大症患者的临床实验室数据时，FGF-23的血清水平也随着垂体手术的降低。这表明FGF-23的分泌迅速响应人类血清磷酸盐水平的降低。