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The analysis of the pathophysiology of MR activation-mediated diabetic nephropathy and the exploration of its novel therapeutic approaches.

Research Project

Project/Area Number 22K20914
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0903:Organ-based internal medicine and related fields
Research InstitutionKeio University

Principal Investigator

Nakamura Toshifumi  慶應義塾大学, 医学部(信濃町), 助教 (10594583)

Project Period (FY) 2022-08-31 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords糖尿病腎症 / ミネラルコルチコイド受容体 / 糖尿病性腎症 / MR拮抗薬
Outline of Research at the Start

我が国における健康寿命・医療経済へ多大な影響を与える糖尿病性腎症の治療法は国内に限らず広く望まれているが、未だ有効な治療法は確立していない。しかし近年の大規模臨床研究FIDELIO-DKDにおいて、Mineralocorticoid receptor (MR)の拮抗薬投与が糖尿病性腎症患者の長期的な生命予後・腎予後を改善することが示され、糖尿病性腎症の病態におけるMR活性の重要性が明らかとなった。本研究では、申請者が先の研究で獲得した糸球体傷害の解析技術および知見を活用・発展させることで、MR活性化を介した糖尿病性腎症の病態を解明し、副作用を回避した新たな治療的アプローチの探索を目指す。

Outline of Final Research Achievements

Using control mice and diabetic model mice, I evaluated renal damage by staining urine albumin and renal tissues for pathological evaluation and gene expression analysis in renal tissues. In diabetic mice, the development of renal damage such as increased urinary albumin levels, mesangial matrix proliferation, inflammatory changes, and fibrosis over time was confirmed. In addition, I confirmed that the expression of MR target genes was upregulated in the diabetic mice. We have now begun a multifaceted analysis of the effects of continuous administration of MR antagonists to diabetic model mice.

Academic Significance and Societal Importance of the Research Achievements

本研究の検討により糖尿病性腎症における病理学的特徴や遺伝子発現変動と、MR拮抗薬によるその変動が示された。今後のさらなる詳細な解析が必要であるが、同定された因子・シグナルへの選択的なアプローチを行うことで、選択性と安全性の高い新たな糖尿病性腎症予防・治療法の確立に貢献できることが期待される。ひいては、本研究による成果は糖尿病性腎症による透析導入患者の減少、進行性に増大する医療費の抑制に大きく寄与するものと考えている。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (3 results)

All 2023 2022

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] The Mineralocorticoid Receptor on Smooth Muscle Cells Promotes Tacrolimus-Induced Renal Injury in Mice2023

    • Author(s)
      Figueroa Stefanny M.、Bertocchio Jean-Philippe、Nakamura Toshifumi、El-Moghrabi Soumaya、Jaisser Frederic、Amador Cristian A.
    • Journal Title

      Pharmaceutics

      Volume: 15 Issue: 5 Pages: 1373-1373

    • DOI

      10.3390/pharmaceutics15051373

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification2022

    • Author(s)
      Jo Rie、Shibata Hirotaka、Kurihara Isao、Yokota Kenichi、Kobayashi Sakiko、Murai-Takeda Ayano、Mitsuishi Yuko、Hayashi Takeshi、Nakamura Toshifumi、Itoh Hiroshi
    • Journal Title

      Hypertension Research

      Volume: 46 Issue: 1 Pages: 19-31

    • DOI

      10.1038/s41440-022-01036-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Presentation] Biglycan, a newly identified mediator of mineralocorticoid receptor activation-induced nephropathy2022

    • Author(s)
      Toshifumi Nakamura, Benjamin Bonnard, Roberto Palacios-Ramirez, Amaya Fernandez-Celis, Frederic Jaisser and Natalia Lopez-Andres
    • Organizer
      The 29th Scientific Meeting of the International Society of Hypertension
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2022-09-01   Modified: 2025-01-30  

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