• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Inhibition of JMJD3 attenuate renal senescense in ischemic reperfusion mice

Research Project

Project/Area Number 16K09618
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionHiroshima University

Principal Investigator

Doi Shigehiro  広島大学, 病院(医), 病院助教 (80626127)

Co-Investigator(Kenkyū-buntansha) 正木 崇生  広島大学, 病院(医), 教授 (30397913)
中島 歩  広島大学, 医歯薬保健学研究科(医), 共同研究講座教授 (40448262)
Research Collaborator UENO Toshinori  
SASAKI Kensuke  
SHIMODA Hironori  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsMLL1 / WDR5 / H3K4me3 / p16INK4a / Senescence / Acute kidney injury / 老化 / p16 / 虚血再灌流障害 / 線維化 / ヒストンメチル化 / ヒストンメチル化酵素 / 腎線維化
Outline of Final Research Achievements

MM-102 suppressed expression of p16INK4a and β-gal in ischemic reperfusion injury (IRI) mice, accompanied by decreased expression of Mixed-lineage leukemia 1 (MLL1) and WD-40 repeat protein 5 (WDR5) as well as H3K4me3. MM-102 also attenuated renal fibrosis and inflammation in the kidneys of IRI mice. In the in vitro study, transforming growth factor-β1 induced expression of MLL1, WDR5, H3K4me3 and p16INK4a. Finally, the p16INK4a promoter was revealed to be an H3K4me3 site in renal fibroblasts.In conclusion, the MLL1/WDR5 inhibitor MM-102 ameliorates IRI-induced renal senescence together with renal fibrosis and inflammation through a reduction in H3K4me3.

Academic Significance and Societal Importance of the Research Achievements

本研究において、腎障害によって惹起されるMixed-lineage leukemia 1 (MLL1)とWD-40 repeat protein 5 (WDR5)の発現亢進によって、H3K4のトリメチル化が起こる結果、腎臓の老化が誘導され、腎における慢性炎症や線維化という病態をきたすことを証明された。この結果、なぜ慢性腎臓病(CKD)における臨床的、病理学的特徴は、加齢腎と一致するのかということが明らかにされた。さらに、CKDを治療する際には、老化に対しても介入しなければ、その進展を完全に抑制することはできないことも認識される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2018

All Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] H3K4 Methyltransferase Inhibitor MM-102 Attenuates Renal Senescence in Ischemic Reperfusion Mice Through Reduction of p16INK4a2018

    • Author(s)
      Hironori Shimoda, Shigehiro Doi, Ayumu Nakashima, Kensuke Sasaki, Toshiki Doi, Takao Masaki
    • Organizer
      Annual Meeting of American Society of Nephrology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] H3K4メチル化酵素阻害剤MM-102は、p16INK4aの発現を抑制し、腎の炎症と線維化を改善する2018

    • Author(s)
      下田大紀、 土井盛博 、 土井俊樹 、 中島歩 、 正木崇生
    • Organizer
      日本腎臓学会
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi