Mechanism of sensing blood phosphorus levels and regulation of FGF23 expression

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16193
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Jichi Medical University
• Principal Investigator: Miura Yutaka 自治医科大学, 医学部, 助教 (20823678)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: リン / FGF23

Outline of Final Research Achievements

The body maintains proper blood phosphorus homeostasis mainly through renal excretion.
Elevated blood phosphorus concentrations are sensed by bone, which increases expression of the phosphorus diuretic hormone, FGF23, which is secreted into the blood and acts on the kidneys to promote phosphorus excretion, but the mechanism of phosphorus sensing by bone and the mechanism of increased FGF23 expression is not yet understood.
In this study, we aim to elucidate the phosphorus sensing mechanism by bone and the molecular basis for the subsequent increase in FGF23 expression, based on the new finding by the applicants that bone senses calcium phosphate, which is formed when phosphorus levels increase, rather than phosphorus itself, and upregulates FGF23 expression. The objective of this project is to elucidate the phosphorus sensing mechanism by bone and the molecular basis for the subsequent increase in FGF23 expression.

Free Research Field

リン代謝

Academic Significance and Societal Importance of the Research Achievements

生体内のリン感知機構についてはリン代謝異常をきたす動物モデルや、関連すると考えられる遺伝子を欠損させた培養細胞などを用いてこれまで多くの研究がなされてきたが、その受容体などそのメカニズムの実態解明には至っていない。本研究では骨においてリン酸カルシウムのシグナルを検討するという点において独創的であり、最先端の研究と位置付けることができると考えられる。