Phosphate-sensing mechanisms and functions of phosphate as a first messenger
Bone secrets the hormone, fibroblast growth factor 23 (FGF23), as an endocrine organ to regulate blood phosphate level. Phosphate is an essential mineral for the human body, and around 85% of phosphate is present in bone as a constituent of hydroxyapatite, Ca10(PO4)6(OH)2. Because hypophosphatemia i...
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The Japan Endocrine Society
2024-04-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/4/71_EJ24-0082/_html/-char/en |
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| author | Yuichi Takashi |
| author_facet | Yuichi Takashi |
| author_sort | Yuichi Takashi |
| collection | DOAJ |
| description | Bone secrets the hormone, fibroblast growth factor 23 (FGF23), as an endocrine organ to regulate blood phosphate level. Phosphate is an essential mineral for the human body, and around 85% of phosphate is present in bone as a constituent of hydroxyapatite, Ca10(PO4)6(OH)2. Because hypophosphatemia induces rickets/osteomalacia, and hyperphosphatemia results in ectopic calcification, blood phosphate (inorganic form) level must be regulated in a narrow range (2.5 mg/dL to 4.5 me/dL in adults). However, as yet it is unknown how bone senses changes in blood phosphate level, and how bone regulates the production of FGF23. Our previous data indicated that high extracellular phosphate phosphorylates FGF receptor 1 (FGFR1) in an unliganded manner, and its downstream intracellular signaling pathway regulates the expression of GALNT3. Furthermore, the post-translational modification of FGF23 protein via a gene product of GALNT3 is the main regulatory mechanism of enhanced FGF23 production due to high dietary phosphate. Therefore, our research group proposes that FGFR1 works as a phosphate-sensing receptor at least in the regulation of FGF23 production and blood phosphate level, and phosphate behaves as a first messenger. Phosphate is involved in various effects, such as stimulation of parathyroid hormone (PTH) synthesis, vascular calcification, and renal dysfunction. Several of these responses to phosphate are considered as phosphate toxicity. However, it is not clear whether FGFR1 is involved in these responses to phosphate. The elucidation of phosphate-sensing mechanisms may lead to the identification of treatment strategies for patients with abnormal phosphate metabolism. |
| format | Article |
| id | doaj-art-0d6eca79ac2e4411995142e1398aa600 |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-0d6eca79ac2e4411995142e1398aa6002025-01-22T06:37:03ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-04-0171433534310.1507/endocrj.EJ24-0082endocrjPhosphate-sensing mechanisms and functions of phosphate as a first messengerYuichi Takashi0Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka 814-0180, JapanBone secrets the hormone, fibroblast growth factor 23 (FGF23), as an endocrine organ to regulate blood phosphate level. Phosphate is an essential mineral for the human body, and around 85% of phosphate is present in bone as a constituent of hydroxyapatite, Ca10(PO4)6(OH)2. Because hypophosphatemia induces rickets/osteomalacia, and hyperphosphatemia results in ectopic calcification, blood phosphate (inorganic form) level must be regulated in a narrow range (2.5 mg/dL to 4.5 me/dL in adults). However, as yet it is unknown how bone senses changes in blood phosphate level, and how bone regulates the production of FGF23. Our previous data indicated that high extracellular phosphate phosphorylates FGF receptor 1 (FGFR1) in an unliganded manner, and its downstream intracellular signaling pathway regulates the expression of GALNT3. Furthermore, the post-translational modification of FGF23 protein via a gene product of GALNT3 is the main regulatory mechanism of enhanced FGF23 production due to high dietary phosphate. Therefore, our research group proposes that FGFR1 works as a phosphate-sensing receptor at least in the regulation of FGF23 production and blood phosphate level, and phosphate behaves as a first messenger. Phosphate is involved in various effects, such as stimulation of parathyroid hormone (PTH) synthesis, vascular calcification, and renal dysfunction. Several of these responses to phosphate are considered as phosphate toxicity. However, it is not clear whether FGFR1 is involved in these responses to phosphate. The elucidation of phosphate-sensing mechanisms may lead to the identification of treatment strategies for patients with abnormal phosphate metabolism.https://www.jstage.jst.go.jp/article/endocrj/71/4/71_EJ24-0082/_html/-char/enbonephosphatefibroblast growth factor 23fibroblast growth factor receptor 1first messenger |
| spellingShingle | Yuichi Takashi Phosphate-sensing mechanisms and functions of phosphate as a first messenger Endocrine Journal bone phosphate fibroblast growth factor 23 fibroblast growth factor receptor 1 first messenger |
| title | Phosphate-sensing mechanisms and functions of phosphate as a first messenger |
| title_full | Phosphate-sensing mechanisms and functions of phosphate as a first messenger |
| title_fullStr | Phosphate-sensing mechanisms and functions of phosphate as a first messenger |
| title_full_unstemmed | Phosphate-sensing mechanisms and functions of phosphate as a first messenger |
| title_short | Phosphate-sensing mechanisms and functions of phosphate as a first messenger |
| title_sort | phosphate sensing mechanisms and functions of phosphate as a first messenger |
| topic | bone phosphate fibroblast growth factor 23 fibroblast growth factor receptor 1 first messenger |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/4/71_EJ24-0082/_html/-char/en |
| work_keys_str_mv | AT yuichitakashi phosphatesensingmechanismsandfunctionsofphosphateasafirstmessenger |