Fibroblast growth factor 23 in renal phosphate reabsorption and vitamin D metabolism

成纤维细胞生长因子 23 在肾脏磷酸盐重吸收和维生素 D 代谢中的作用

• 批准号: 14370320
• 负责人: MIYAMOTO Kenichi
• 金额: $ 9.09万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370320/
• 关键词: FGF23; phosphate; kidney; phosphatonin; receptor; Brain

Fibroblast growth factor 23 (FGF23), a phosphaturic factor, is involved in the regulation of renal Pi reabsocption. Proteolysis-resistant FGF23 mutants expressed in rodents reduce Pi uptake in both intestine and kidney, independent of parathyroid hormone action. In the present study, we investigated whether FGF23 affect dietary regulation of Na^+-dependent Pi (Na/Pi) cotransport in rat kidney using wild-type FGF23 and an R 179Q mutant, which disrupts a consensus proteolytic cleavage motifRats injected with naked human FGF23 DNA (wild type or R 179Q mutant) expressed human FGF23 transcript in the liver. In those animals, the plasma calcium and parathyroid hormone levels were not affected by FGF23 (either wild type or R179Q mutant). FGF23-R179Q did, however, significantly decrease the plasma Pi and renal Na/Pi cotransport activity and also the levels of type IIc Na/Pi cotransporter proteins in BBMVs from normal rat kidney. In rats fed a low Pi diet, the levels of type IIa and type IIc Na/Pi cotransporters were markedly ink in Western blotting and immunohistochemical analyses. After injection of FGF23-R 179Q DNA into the rats fed a low Pi diet, the levels of the type IIa and type IIc transporter proteins were decreased. Thus FGF23 mutant blunts the signaling of Pi deprivation in renal type II Na/Pi cotransporters, suggesting that the FGF23 pathway could be involved in the signaling of dietary Pi

成纤维细胞生长因子23（FGF23）是一种磷酸因子，参与了肾脏PI重吸收的调节。在啮齿动物中表达的抗蛋白水解的FGF23突变体降低了肠和肾脏中的PI摄取，与甲状旁腺激素作用无关。在本研究中，我们研究了FGF23是否影响了使用野生型FGF23和R 179Q突变体在大鼠肾脏中Na^+ - 依赖性PI（Na/pi）共转移的饮食调节，这破坏了naked Human Fgf23 dna（wirderf23 dna dna dna dna dna99999999999999），破坏了蛋白水解的蛋白水解蛋白水解突变（在肝脏中。在这些动物中，血浆钙和甲状旁腺激素水平不受FGF23（野生型或R179Q突变体）的影响。但是，FGF23-R179Q确实显着降低了血浆PI和肾脏Na/Pi共转运活性，以及​​来自正常大鼠肾脏中BBMV中IIC Na/Pi cotransporter蛋白的水平。在喂养PI饮食的大鼠中，IIA型和IIC型Na/Pi cotransporters的水平显然是蛋白质印迹和免疫组织化学分析的墨水。将FGF23-R 179Q DNA注射到喂养低PI饮食的大鼠中后，IAIA型和IIC型转运蛋白蛋白的水平降低了。因此，FGF23突变体在肾脏II型Na/Pi共转运蛋白中的PI剥夺信号传导，这表明FGF23途径可能参与饮食PI的信号

项目成果

Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, Miyamoto K, Fukushima N.: "Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1 α, 25dihydroxyvitamin D3 production"J Biol Chem. 278. 2206-2211 (20

Saito H、Kusano K、Kinosaki M、Ito H、Hirata M、Sekawa H、Miyamoto K、Fukushima N.：“人成纤维细胞生长因子-23 突变体抑制 Na+ 依赖性磷酸盐共转运活性和 1 α, 25 二羟基维生素 D3 的产生”生物化学杂志 278。2206-2211 (20

Segawa H.: "Growth-related renal type II Na/Pi contransporter"J Biol Chem. 277. 19665-19672 (2002)

Sekawa H.：“生​​长相关的肾 II 型 Na/Pi 转运蛋白”J Biol Chem。

桑波田 雅士: "リン代謝の最近の理解とリン調節薬の将来、透析療法ネクストII透析骨症は防げる"43-48 (2003)

Masashi Kuwabata：“磷代谢的最新认识和磷调节药物的未来，透析疗法 NEXT II 透析骨病是可以预防的”43-48 (2003)

Ohkido I, Segawa H, Yanagida R, Nakamura M, Miyamoto K.: "Cloning, gene structure and dietary regulation of the type-IIc Na/Pi cotransporter in the mouse kidney"Pflugers Arch.2003 Apr. 446(1). 106-115 (2003)

Ohkido I、Sekawa H、Yanagida R、Nakamura M、Miyamoto K.：“小鼠肾脏中 IIc 型 Na/Pi 协同转运蛋白的克隆、基因结构和饮食调节”Pflugers Arch.2003 Apr. 446(1)。

Saito H: "Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1α, 25-dihydroxyvitamin D3 production"J Biol Chem. 278. 2206-2211 (2003)

Saito H：“人成纤维细胞生长因子-23 突变体抑制 Na+ 依赖性磷酸盐共转运活性和 1α, 25-二羟基维生素 D3 的产生”J Biol Chem. 278. 2206-2211 (2003)