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Association between complement activation pathways and nonalcoholic fatty liver disease

Research Project

Project/Area Number 18K15789
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionFukushima Medical University

Principal Investigator

Hayashi Manabu  福島県立医科大学, 医学部, 助教 (80745787)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Keywords脂肪肝 / 補体 / MASP / MASP-1 / MASP-3 / 線維化 / 非アルコール性脂肪肝疾患 / 非アルコール性脂肪肝炎
Outline of Final Research Achievements

We investigated the role of MASP-1 and MASP-3 in complement activation pathway using MASP-1 deficient mice and MASP-3 deficient mice. We revealed that MASP-3 is an alternative pathway-specific serine protease, whereas MASP-1 is an lectin pathway-specific serine protease. Further, we investigated the role of MASP-1 and MASP-3 in nonalcoholic fatty liver disease. Our Oil Red O staining of hepatic lipids revealed that decrease of liver steatosis in MASP-3 deficient mice. MASP-3 deficient mice also showed low serum ALT and low expression of Col1a1 in the liver compared with wild type mice. These findings suggested that MASP-3 deficient play protective role for NAFLD in mice.

Academic Significance and Societal Importance of the Research Achievements

非アルコール性脂肪肝疾患(NAFLD)はメタボリックシンドロームの肝臓における病態であるが、有病率が高く、また肝不全へ進行するため、新たな治療方法が必要とされている。補体は生体の恒常性維持のために重要な自然免疫因子であり、MASP-1とMASP-3はそれぞれ異なる補体活性化経路の重要な活性化因子であることを明らかにした。また補体第二経路の活性化因子であるMASP-3の欠損がNAFLD病態に保護的に作用する結果が得られた。本研究は補体の特に第二経路を標的とした治療方法の創出に役立つものと考える。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report

Research Products

(1 results)

All 2019

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Cutting Edge: Role of MASP-3 in the physiological activation of factor D of the alternative complement pathway2019

    • Author(s)
      Manabu Hayashi, Takeshi Machida, Yumi Ishida, Yusuke Ogata, Tomoko Omori, Mika Takasumi, Yuichi Endo, Toshiyuki Suzuki, Masayuki Sekimata, Yoshimi Homma, Masahito Ikawa, Hiromasa Ohira, Teizo Fujita, and Hideharu Sekine
    • Journal Title

      the J Immunol

      Volume: 203 Pages: 1411-1416

    • DOI

      10.4049/jimmunol.1900605

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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