Development of megalin-targeted strategies for diagnosis, prevention, and treatment of chronic kidney disease and acute kidney injury

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02825
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Niigata University
• Principal Investigator: Saito Akihiko 新潟大学, 医歯学総合研究科, 特任教授 (80293207)
• Co-Investigator(Kenkyū-buntansha): 細島 康宏 新潟大学, 医歯学総合研究科, 特任准教授 (50464003) ; 桑原 頌治 新潟大学, 医歯学総合研究科, 特任助教 (70645209)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: メガリン / 慢性腎臓病 / 急性腎障害 / バイオマーカー / 創薬

Outline of Final Research Achievements

The proximal tubular endocytosis receptor, megalin, is involved in the reabsorption and metabolism of various proteins, peptides, and drugs that are filtrated through the glomerulus. In this study, we have investigated (1) the mechanism of urinary megalin excretion and its diagnostic significance, (2) issues for the establishment of megalin suppression therapy to prevent the development and progression of chronic kidney disease: (2)-① the involvement of megalin in the renal renin-angiotensin system (RAS), (2)-② the effect of megalin suppression at different sites in the proximal tubule, (3) issues for the establishment of megalin antagonist therapy for the prevention of acute kidney injury: (3)-① the significance of megalin antagonist therapy for prevention of contrast-induced nephropathy, and (3)-② screening systems for novel megalin antagonists.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

腎臓の近位尿細管細胞膜に存在するメガリンは、糸球体を濾過する様々なタンパク質・ペプチド・薬物等の取り込み・代謝に関わる。メガリンは慢性腎臓病や急性腎障害を引き起こす腎障害性物質を腎臓に取り込む「入り口」としても働くことから、私たちは、病態に応じてメガリンの働きを適切に調節して、そのような物質の腎取り込みを抑制し、腎臓病を軽減する治療法の確立を進めた。さらに、尿中に逸脱するメガリンを腎臓病の検査に応用するための研究も行った。