| Project/Area Number |
18K15980
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Fukuoka University (2019)
The University of Tokushima (2018) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | リン / 線維芽細胞増殖因子23 / 線維芽細胞増殖因子受容体1 / 慢性腎臓病 / FGF23 / FGFR1 / リン感知機構 / 骨細胞 |
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| Outline of Final Research Achievements |
Phosphate plays essential roles in many biological processes. Serum phosphate level needs to be regulated because hypophosphatemia and hyperphosphatemia cause rickets/osteomalacia and ectopic calcification, respectively. Fibroblast growth factor (FGF) 23 is the principal hormone to regulate serum phosphate level. However, it has been unclear how the the bone senses the changes of serum phosphate level and how the bone regulates the production of FGF23. In this study, we indicated that high extracellular phosphate activates FGF receptor (FGFR) 1 via phospho-proteomic approach. In addition, we analyzed the bone-specific FGFR1-deficient mice and showed the significance of FGFR1 in the regulation of FGF23 and phosphate level in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
生体のリン感知機構は未解明の課題である。本研究成果は、世界に先駆けて骨のリン感知機構の分子基盤を明らかにするものである。本邦に1330万人もの罹患患者がいるとされる慢性腎臓病患者において、慢性の高リン血症により惹起される血管石灰化は、罹患患者の死因に直結している。本研究成果は、慢性腎臓病患者の二次性副甲状腺機能亢進症や血管石灰化に対する新たな治療戦略の開発につながる可能性がある。
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