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Development of new CKD therapeutic agent targeting cytokine processing enzyme

Research Project

Project/Area Number 17K09700
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionThe University of Tokushima

Principal Investigator

TOMINAGA Tatsuya  徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (80425446)

Co-Investigator(Kenkyū-buntansha) 安部 秀斉  徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (60399342)
長井 幸二郎  徳島大学, 病院, 講師 (40542048)
藤田 結衣  一般財団法人生産開発科学研究所, 腎病態解析研究室, 学術員 (30837266)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords糖尿病性腎症 / 慢性腎臓病 / サイトカイン / BMP4 / ポドサイト障害 / PACE4 / 糖尿病
Outline of Final Research Achievements

Bone Morphogenetic Protein 4 (BMP4) signal acts on the development of diabetic nephropathy. The glomerular constituent cells were analyzed and the therapeutic effect of BMP4 protease enzyme was examined. A processing inhibitor compound was administered to a type 2 diabetes model (db / db). The mice showed amelioration in urinary protein and BUN and suppression of glomerular mesangial matrix hyperplasia. Precursor BMP4 is modified to become active BMP4 in podocyte cells. It is considered that the processing inhibitor blocked the modification of active BMP4 and suppressed the development of diabetic nephropathy.

Academic Significance and Societal Importance of the Research Achievements

CKDのスタンダードな治療法であるレニン-アンジオテンシン系の阻害薬では、進行を抑えるだけで未だ根治できる治療薬は見つかっていない。糖尿病性腎症への特異性を追求するため、糸球体構成細胞ごとに検証を行い、腎機能低下に直結する分子と分子標的治療について良好な結果を得た。これは、病態の理解と実臨床上も意義が大きい。サイトカインプロセシング酵素を対象にした新規薬剤は、BMP4をピンポイントで不活化し病態進行を抑える効果があり、新たな細胞特異性の高い治療薬として現状抱えている問題を解決できると考えている。

Report

(2 results)
  • 2019 Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (2 results)

All 2017

All Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] Palovarotene, selective retinoic receptor-γ agonist, inhibited both BMP4 and TGF-β signaling pathways in diabetic nephropathy2017

    • Author(s)
      Yui Fujita, Tatsuya Tominaga, Masanori Tamaki, Taichi Murakami, Seiji Kishi, Kojiro Nagai, Hideharu Abe, Toshio Do1
    • Organizer
      The American Society of Nephrology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of BMP4 signal pathway on the glomerulosclerosis.2017

    • Author(s)
      Tatsuya Tominaga, Yui Fujita, Taichi Murakami, Seiji Kishi, Kojiro Nagai, Hideharu Abe, Toshio Doi
    • Organizer
      Keystone symposia
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2025-01-30  

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