Elucidation of a novel phosphate metabolism regulatory mechanism based on megalin involving a-klotho and FGF23

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08674
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: The University of Shiga Prefecture
• Principal Investigator: Kuwahara Shoji 滋賀県立大学, 人間文化学部, 准教授 (70645209)
• Co-Investigator(Kenkyū-buntansha): 斎藤 亮彦 新潟大学, 医歯学総合研究科, 特任教授 (80293207)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: メガリン / 慢性腎臓病 / リン代謝

Outline of Final Research Achievements

The global prevalence of chronic kidney disease (CKD) is on the rise. As kidney function declines due to CKD, alternative therapies become necessary, with hemodialysis being the predominant method in Japan. It has been shown that hemodialysis leads to a shortened healthy lifespan, decreased QOL, and increased medical costs. Therefore, it is an urgent task to prevent the need for renal replacement therapies by curbing the decline in kidney function. One of the major factors shortening the lifespan of CKD patients undergoing dialysis is cardiovascular disease associated with high blood phosphate levels. However, many aspects of the regulatory mechanisms of blood phosphate levels remain unclear. This study aims to demonstrate a novel phosphate metabolism regulatory mechanism in the kidneys, which is expected to provide a foundation for the development of new therapies.

Free Research Field

腎臓、臨床栄養、栄養代謝

Academic Significance and Societal Importance of the Research Achievements

血中リン濃度の上昇はリン利尿因子の増加を引き起こし、尿中にリンを積極的に排泄することで血中濃度を下げる効果がある。強力なリン利尿効果を持つ線維芽細胞増殖因子23（FGF23）が同定されており、これも尿中リン排泄を促進する。しかしFGF23はその差要点である受容体が主に腎臓の遠位尿細管に局在しており、主要なリン輸送体は近位尿細管に発現するというある種の矛盾があった。またFGF23の共受容体として必要である老化関連因子α-klothoも主に遠位尿細管に発現している。本研究では近位尿細管のメガリンを介するFGF23やα-klotho作用の可能性を示したものであり、新規治療戦略の開発が期待される。