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Direct Contribution of Mitochondorial Oxidative Stress to Hepatic Fibrogenesis

Research Project

Project/Area Number 24659376
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionTokai University

Principal Investigator

INAGAKI Yutaka  東海大学, 医学部, 教授 (80193548)

Co-Investigator(Kenkyū-buntansha) ISHII Naoaki  東海大学, 医学部, 教授 (60096196)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords酸化ストレス / 肝線維化 / マクロファージ / 非アルコール性脂肪肝炎 / 肝線維症 / コラーゲン遺伝子
Research Abstract

Oxidative stress is considered to play a key role in the progression of chronic liver diseases. However, since production of oxidative stress may merely represent the consequences of cell damage and subsequent inflammation, it is virtually unknown whether oxidative stress is linked directly to fibrogenesis.
Hepatocytes isolated from Tet-mev-1 mouse, in which mitochondrial reactive oxygen species can be induced, exhibited decreased mitochondrial membrane potential. Tet-mev-1 mice were fed high fat/high sucrose (HFHS)diet, and microarray analyses indicated that CC chemokine expression was remarkably elevated in the liver tissue. However, the number of F4/80-positive cells was substantially decreased, and there was no
apparent liver fibrosis observed in Tet-mev-1 mice fed HFHS diet. These results suggested the important role of macrophages in the progression of liver fibrosis.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (45 results)

All 2014 2013 2012 Other

All Journal Article (17 results) (of which Peer Reviewed: 11 results) Presentation (22 results) (of which Invited: 1 results) Book (1 results) Remarks (5 results)

  • [Journal Article] Mechanisms of action of acetaldehyde in the up regulation of the human 2(I) collagen gene in hepatic stellate cells-key roles of Ski, SMAD3, SMAD4 and SMAD72014

    • Author(s)
      Karina Reyes-Gordillo, Ruchi Shah, Jaime Arellanes-Robledo, Zamira Hernández-Nazara, Ana Rosa Rincón-Sánchez, Yutaka Inagaki, Marcos Rojkind, M. Raj Lakshman
    • Journal Title

      Am J Pathol

      Volume: in press Issue: 5 Pages: 1458-1467

    • DOI

      10.1016/j.ajpath.2014.01.020

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel small compound accelerates dermal wound healing by modifying infiltration, proliferation and migration of distinct cellular components in mice2014

    • Author(s)
      Yamaoka H, Sumiyoshi H, Higashi K, Nakao S, Minakawa K, Sumida K, Saito K, Ikoma N, Mabuchi T, Ozawa A, and Inagaki Y.
    • Journal Title

      J Dermatol Sci 2014

      Volume: (in press) Issue: 3 Pages: 204-213

    • DOI

      10.1016/j.jdermsci.2014.03.002

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fibrogenesis and carcinogenesis in nonalcoholic steatohepatitis (NASH) : Involvement of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs)2014

    • Author(s)
      Okazaki I, Noro T, Tsutsui N, Yamanouchi E, Kuroda H, Nakano M, Yokomori H, and Inagaki Y.
    • Journal Title

      Cancers 2014

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stem and Progenitor Cell Systems in Liver Development and Regeneration2014

    • Author(s)
      Kamiya A and Inagaki Y.
    • Journal Title

      Hepatol Res 2014

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 肝線維化改善の分子・細胞基盤2014

    • Author(s)
      稲垣 豊、茂呂 忠、住吉秀明
    • Journal Title

      肝胆膵

      Volume: in press

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Fibrogenesis and Carcinogenesis in NASH: Role of MMPs and TIMPs2014

    • Author(s)
      Isao Okazaki, Takufumi Noro, Eigoro Yamanouchi, Hajime Kuroda, Masayuki Nakano, Hiroaki Yokomori, Yutaka Inagaki
    • Journal Title

      Cancers

      Volume: in press

    • Related Report
      2013 Annual Research Report
  • [Journal Article] ERK-dependent downregulation of Skp2 reduces Myc activity with HGF, leading to inhibition of cell proliferation through a decrease in Id1 expression2013

    • Author(s)
      Li, X., Bian, Y., Takizawa, Y., Hashimoto, T., Ikoma, T., Tanaka, J., Kitamura, N., Inagaki, Y., Komada, M., and Tanaka, T.
    • Journal Title

      Mol. Cancer Res.

      Volume: 11 Issue: 11 Pages: 1437-1447

    • DOI

      10.1158/1541-7786.mcr-12-0718

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Qualitative Rather than Quantitative Changes Are Hallmarks of Fibroblasts in Bleomycin-Induced Pulmonary Fibrosis2013

    • Author(s)
      Tatsuya Tsukui, Satoshi Ueha, Jun Abe, Shin-ichi Hashimoto, Shigeyuki Shichino, Takeshi Shimaoka, Francis H. W. Shand, Yasuka Arakawa, Kenshiro Oshima, Masahira Hattori, Yutaka
    • Journal Title

      The American Journal of Pathology

      Volume: 3 Issue: 3 Pages: 758-773

    • DOI

      10.1016/j.ajpath.2013.06.005

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] マウス皮膚創傷治癒モデルにおける筋膜由来線維芽細胞と希少コラーゲンのはたらき2013

    • Author(s)
      住吉秀明、稲垣 豊
    • Journal Title

      食品加工技術

      Volume: 33 Pages: 124-130

    • NAID

      40019805327

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 今なぜ肝線維化研究が注目されているのか.2013

    • Author(s)
      稲垣 豊
    • Journal Title

      医学のあゆみ

      Volume: 244 Pages: 513-513

    • Related Report
      2012 Research-status Report
  • [Journal Article] コラーゲン分子種と線維症形成へのかかわり.2013

    • Author(s)
      住吉秀明
    • Journal Title

      医学のあゆみ

      Volume: 244 Pages: 515-520

    • Related Report
      2012 Research-status Report
  • [Journal Article] Novel strategies for hepatocellular carcinoma based on MMPs science2012

    • Author(s)
      Okazaki I and Inagaki Y.
    • Journal Title

      Anti-Cancer Agents Med Chem

      Volume: 12 Pages: 753-763

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interplay between bone marrow and liver in the pathogenesis of hepatic fibrosis2012

    • Author(s)
      Inagaki Y and Higashiyama R.
    • Journal Title

      Hepatol Res

      Volume: 42 Pages: 543-548

    • NAID

      10031144268

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel anti-fibrotic modalities for liver fibrosis : Molecular targeting and regenerative medicine in fibrosis therapy2012

    • Author(s)
      Inagaki Y, Higashiyama R, and Higashi K.
    • Journal Title

      J Gastroenterol Hepatol

      Volume: 27 Pages: 85-88

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interplay between bone marrow and liver in the pathogenesis of hepatic fibrosis.2012

    • Author(s)
      Yutaka Inagaki
    • Journal Title

      Hepatol Res

      Volume: 42 Issue: 6 Pages: 543-548

    • DOI

      10.1111/j.1872-034x.2012.00978.x

    • NAID

      10031144268

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel strategies for hepatocellular carcinoma based on MMPs science.2012

    • Author(s)
      Isao Okazaki
    • Journal Title

      Anti-Cancer Agents Med Chem

      Volume: 12 Pages: 753-763

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 肝線維症治療の研究はどこまで進展したか?2012

    • Author(s)
      稲垣 豊
    • Journal Title

      肝胆膵

      Volume: 65 Pages: 253-260

    • Related Report
      2012 Research-status Report
  • [Presentation] Direct contribution of mitochondrial oxidative stress to hepatic fibrogenesis2013

    • Author(s)
      Moro T, Nakao S, Sumiyoshi H, Ishii T, Miyazawa M, Ishii N, and Inagaki Y.
    • Organizer
      64th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Washington DC
    • Year and Date
      2013-11-03
    • Related Report
      2013 Final Research Report
  • [Presentation] Mitochondrial oxidative stress exacerbates inflammation and subsequent fibrogenesis in high fat diet-induced murine hepatic steatosis2013

    • Author(s)
      Moro T, Nakao S, Sumiyoshi H, Ishii T, Miyazawa M, Ishii N, and Inagaki Y.
    • Organizer
      17th International Symposium on Cells of the Hepatic Sinusoid
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2013-09-25
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリア由来活性酸素惹起モデルマウスを用いた酸化ストレスによる肝線維化促進機序の解明2013

    • Author(s)
      茂呂忠、中尾祥絵、住吉秀明、宮沢正樹、石井恭正、石井直明、稲垣豊
    • Organizer
      第45回日本結合組織学会学術大会・第60回マトリックス研究会大会合同学術大会
    • Place of Presentation
      和歌山
    • Year and Date
      2013-06-28
    • Related Report
      2013 Final Research Report
  • [Presentation] 線維肝の再生における骨髄と肝臓の臓器相関2012

    • Author(s)
      稲垣豊
    • Organizer
      第11回日本再生医療学会総会、シンポジウム5「臓器再生の名脇役達-血管再生と炎症・間質組織の生理学的および病理学的役割-」
    • Place of Presentation
      横浜
    • Year and Date
      2012-06-14
    • Related Report
      2013 Final Research Report
  • [Presentation] 細胞系譜特異的Notch/Jagged-1シグナルによる肝線維化と前駆細胞動員の制御機構

    • Author(s)
      住吉秀明、三上健一郎、茂呂 忠、紙谷聡英、稲垣 豊
    • Organizer
      第49回日本肝臓学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 新規低分子化合物HSc025は細胞増殖と遊走を活性化して創傷治癒を促す

    • Author(s)
      住吉秀明、山岡華児、中尾祥絵、生駒憲広、馬渕智生、小澤 明、東 清史、斎藤幸一、稲垣 豊
    • Organizer
      第45回日本結合組織学会学術大会、第60回マトリックス研究会大会合同学術大会
    • Place of Presentation
      和歌山
    • Related Report
      2013 Annual Research Report
  • [Presentation] 胆汁うっ滞型肝線維症におけるコラーゲン産生細胞の起源と初期動態

    • Author(s)
      中尾祥絵、茂呂 忠、住吉秀明、稲垣 豊
    • Organizer
      第45回日本結合組織学会学術大会、第60回マトリックス研究会大会合同学術大会
    • Place of Presentation
      和歌山
    • Related Report
      2013 Annual Research Report
  • [Presentation] ミトコンドリア由来活性酸素惹起モデルマウスを用いた酸化ストレスによる肝線維化促進機序の解明

    • Author(s)
      茂呂 忠、中尾祥絵、住吉秀明、宮沢正樹、石井恭正、石井直明、稲垣 豊
    • Organizer
      第45回日本結合組織学会学術大会、第60回マトリックス研究会大会合同学術大会
    • Place of Presentation
      和歌山
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mitochondrial oxidative stress exacerbates inflammation and subsequent fibrogenesis in high fat diet-induced murine hepatic steatosis

    • Author(s)
      Tadashi Moro, Sachie Nakao, Hideaki Sumiyoshi, Takamasa Ishii, Masaki Miyazawa, Naoaki Ishii, Yutaka Inagaki
    • Organizer
      17th International Symposium on Cells of the Hepatic Sinusoid
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] Identification of a novel bone marrow cell-derived factor that suppresses fibrogenesis and accelerates regeneration of murine fibrotic liver

    • Author(s)
      Hideaki Sumiyoshi, Hiroshi Fukumitsu, Reiichi Higashiyama, Sachie Nakao, Kaori Minakawa, Minako Sueoka, Hiromi Chikada, Akihide Kamiya, Kiyoshi Higashi, Koichi Saito, Yutaka Inagaki
    • Organizer
      The 20th Annual Meeting of the Japanese Society for the Research of Hepatic Cells
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] Direct contribution of mitochondrial oxidative stress to hepatic fibrogenesis

    • Author(s)
      Tadashi Moro, Sachie Nakao, Hideaki Sumiyoshi, Takamasa Ishii, Masaki Miyazawa, Naoaki Ishii, Yutaka Inagaki
    • Organizer
      64th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      ワシントンDC
    • Related Report
      2013 Annual Research Report
  • [Presentation] Pirin誘導低分子化合物Hsc025は細胞増殖と遊走を活性化して創傷治癒を促す

    • Author(s)
      住吉秀明、山岡華児、中尾祥絵、生駒憲広、馬渕智生、小澤 明、東 清史、斎藤幸一、稲垣 豊
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 骨髄細胞に由来する新たな肝線維化改善・再生促進因子の同定と臨床応用.

    • Author(s)
      福光 寛
    • Organizer
      第48回肝臓学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Research-status Report
  • [Presentation] 胆汁うっ滞型肝線維症におけるコラーゲン産生細胞の起源と初期動態.

    • Author(s)
      茂呂 忠
    • Organizer
      第48回肝臓学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Research-status Report
  • [Presentation] Notch/Jagged-1シグナルを介した肝前駆細胞動員と線維化の制御機構.

    • Author(s)
      三上健一郎
    • Organizer
      第48回肝臓学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Research-status Report
  • [Presentation] 骨髄細胞に由来する新たな肝線維化改善・再生促進因子の同定と臨床応用.

    • Author(s)
      住吉秀明
    • Organizer
      第11回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 線維肝の再生における骨髄と肝臓の臓器相関.

    • Author(s)
      稲垣 豊
    • Organizer
      第11回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Hepatocyte growth factor (HGF)による細胞増殖制御機構の解明.

    • Author(s)
      瀧澤友里
    • Organizer
      第19回肝細胞研究会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] Identification of a novel bone marrow cell-derived factor that suppresses fibrogenesis and accelerates regeneration of murine fibrotic liver.

    • Author(s)
      Yutaka Inagaki
    • Organizer
      63rd Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston
    • Related Report
      2012 Research-status Report
  • [Presentation] 胆汁うっ滞型肝線維症におけるコラーゲン産生細胞の起源と初期動態.

    • Author(s)
      茂呂 忠
    • Organizer
      第26回肝類洞壁細胞研究会学術集会
    • Place of Presentation
      宇部
    • Related Report
      2012 Research-status Report
  • [Presentation] 細胞種特異的Notchシグナルによる肝線維化と再生の病態連繋.

    • Author(s)
      瀧澤友里
    • Organizer
      第26回肝類洞壁細胞研究会学術集会
    • Place of Presentation
      宇部
    • Related Report
      2012 Research-status Report
  • [Presentation] 細胞系譜特異的Notch/Jagged-1シグナルによる肝線維化と再生の病態形成.

    • Author(s)
      住吉秀明
    • Organizer
      第12回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Book] 日本肝臓学会創立50周年記念誌2014

    • Author(s)
      稲垣 豊
    • Publisher
      日本肝臓学会
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.u-tokai.ac.jp/daigakuin/pdf/inagaki_yutaka_2014_04_01.pdf

    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www.med.u-tokai.ac.jp/daigakuin/web/matrix.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 東海大学大学院医学研究科

    • URL

      http://www.med.u-tokai.ac.jp/daigakuin/pdf/inagaki_yutaka_2014_04_01.pdf

    • Related Report
      2013 Annual Research Report
  • [Remarks] 東海大学大学院医学研究科マトリックス医学生物学センター

    • URL

      http://www.med.u-tokai.ac.jp/daigakuin/web/matrix.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 東海大学大学院医学研究科研究者一覧

    • URL

      http://www.med.u-tokai.ac.jp/daigakuin/pdf/inagaki_yutaka_2013_04_01.pdf

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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