Regulation of calcium and phosphate metabolism by inorganic phosphate sensor (type IIc Na/Pi cotransporter)

无机磷酸盐传感器（IIc型Na/Pi协同转运蛋白）调节钙和磷酸盐代谢

• 批准号: 16390244
• 负责人: MIYAMOTO Ken-ichi
• 金额: $ 9.34万
• 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: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390244/
• 关键词: FGF23; phosphate; kidney; phosphatonin; sensor; phosphate; kidney; phosphatonin; receptor

Phosphate ions ate critical for normal bone mineralization, and phosphate plays a vital role in a number of other biological processes such as signal transduction, nucleotide metabolism, and enzyme regulation. In the present study, we have cloned a putative inorganic phosphate sensor (type IIc Na/Pi cotransporter) that is expressed in kidney, bone and brain. A novel phosphaturic factor, fibroblast growth factor 23,decreased the expression of inorganic phosphate sensor (type IIc) in the kidney. We demonstrated that klotho and FGF23 functions via a common signaling pathway. FGF23 binds to the klotho/FGF receptor (FGFR) complex with higher affinity than it binds to FGFR or klotho alone. In addition, klotho significantly enhances the ability of FGF23 to induce phosphorylation of an FGF receptor substrate and ERK in various types of cells, suggesting that klotho functions as a cofactor essential for activation of FGF signaling by FGF23. Finally, we demonstrated that FGF23/klotho signaling is necessary to regulate the expression of inorganic phosphate sensor (type IIc) in the kidney and bone.

磷酸盐离子对正常的骨矿化至关重要，并且磷酸盐在许多其他生物过程中起着至关重要的作用，如信号转导、核苷酸代谢和酶调节。在本研究中，我们克隆了一个假定的无机磷酸盐传感器（IIc型Na/Pi协同转运蛋白），在肾脏，骨骼和大脑中表达。一种新的磷酸尿因子，成纤维细胞生长因子23，降低了肾脏中无机磷酸盐传感器（IIc型）的表达。我们证明了klotho和FGF 23通过共同的信号传导途径发挥作用。FGF 23以比其单独结合FGFR或klotho更高的亲和力结合klotho/FGF受体（FGFR）复合物。此外，klotho显著增强了FGF 23在各种类型的细胞中诱导FGF受体底物和ERK磷酸化的能力，表明klotho作为FGF 23激活FGF信号传导所必需的辅因子发挥作用。最后，我们证明了FGF 23/klotho信号传导对于调节肾脏和骨骼中无机磷酸盐传感器（IIc型）的表达是必要的。

项目成果

遺伝性低リン血症くる病

遗传性低血磷性佝偻病

• 发表时间: 2005
• 期刊: 腎と透析 58(3)
• 作者: Saito H;Ito M;Ito M;Miyamoto K;Nashiki K;宮本賢一.;山中説子.;宮本賢一.;宮本賢一.;宮本賢一.
• 通讯作者: 宮本賢一.

Approach to novel functional foods for stress control 4. Regulation of serotonin transport by food factors.

用于压力控制的新型功能食品的方法4.食物因素对血清素运输的调节。

• 发表时间: 2005
• 期刊: J Med Invest. 52
• 作者: Ito M;Haito S;Furumoto M;Kawai Y;Terao J;Miyamoto K.
• 通讯作者: Miyamoto K.

リンバランスの調節機構.

磷平衡的调节机制。

• 发表时间: 2004
• 期刊: 透析会誌 37(12)
• 作者: Segawa H;Furutani J;Miyamoto K.;Segawa H;Saito H;Ito M;Ito M;Matsuo A;Miyamoto K;Segawa H;Ito M;Yamamoto H;Miyamoto K;Segawa H;宮本賢一;宮本賢一;宮本賢一;山中説子;宮本賢一;瀬川博子;Ito M;Ito M;Miyamoto K;Segawa H;Segawa H;宮本賢一.;宮本賢一.;宮本賢一.;瀬川博子.
• 通讯作者: 瀬川博子.

Role of the vitamin D receptor in FGF23 action on phosphate metabolism

• DOI: 10.1042/bj20041799
• 发表时间: 2005-08-15
• 期刊: BIOCHEMICAL JOURNAL
• 影响因子: 4.1
• 作者: Inoue, Y;Segawa, H;Miyamoto, K
• 通讯作者: Miyamoto, K

Internalization of renal type IIc Na-Pi cotransporter in response to a high-phosphate diet.

• DOI: 10.1152/ajprenal.00097.2004
• 发表时间: 2005-03
• 期刊: American journal of physiology. Renal physiology
• 作者: H. Segawa;S. Yamanaka;Mikiko Ito;M. Kuwahata;M. Shono;Tadashi Yamamoto;K. Miyamoto