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Comprehensive Analysis of Production and Degradation of Collagen by Bone Marrow-Derived Cells During Hepatic Fibrogenesis

Research Project

Project/Area Number 19590792
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTokai University

Principal Investigator

INAGAKI Yutaka  Tokai University, 医学部, 教授 (80193548)

Co-Investigator(Kenkyū-buntansha) 東山 礼一  東海大学, 医学部, 奨励研究員 (80459495)
Co-Investigator(Renkei-kenkyūsha) HIGASHIYAMA Reiichi  東海大学, 医学部, 奨励研究員 (80459495)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords肝線維症 / コラーゲン / Matrix metalloproteinase / 肝線維化 / マトリックス分解酵素 / 骨髄細胞 / コラゲナーゼ / マトリックスメタロプロテアーゼ / 星細胞 / 分化誘導
Research Abstract

肝炎ウイルス感染やアルコールの過剰摂取・肥満など、様々な原因で肝臓の線維化が引き起こされる際には、肝組織中にコラーゲンが過剰に蓄積する。組織におけるコラーゲンの含有量は合成系と分解系の適切なバランスの上に維持されているが、両者の調節機構は不明であった。そこで本研究では、コラーゲンとその分解酵素の両遺伝子を組み込んだ遺伝子改変マウスを作製して、肝線維化の進展過程における両遺伝子の発現動態を明らかにした。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (51 results)

All 2008 2007 Other

All Journal Article (18 results) (of which Peer Reviewed: 15 results) Presentation (31 results) Remarks (2 results)

  • [Journal Article] Hepatocyte growth factor suppresses profibrogenic signal transduction via nuclear export of Smad3 with galectin-72008

    • Author(s)
      Inagaki Y, Higashi K, Higashiyama R, 他10名
    • Journal Title

      Gastroenterology 134

      Pages: 1180-1190

    • NAID

      40016346603

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glycyrrhizin and its metabolite inhibit Smad3-mediated type I collagen gene transcription and suppress experimental murine liver fibrosis2008

    • Author(s)
      Moro T, Higashiyama R, Inagaki Y, 他7名
    • Journal Title

      Life Sciences 83

      Pages: 531-539

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 肝線維化機序の解明で今何が問題になっているのか2008

    • Author(s)
      稲垣豊、東山礼一
    • Journal Title

      肝胆膵 57

      Pages: 187-192

    • Related Report
      2008 Final Research Report
  • [Journal Article] Hepatocyte growth factor suppresses profibrogenic signal transduction via nuclear export of Smad3 with galectin-7.2008

    • Author(s)
      Yutaka Inagaki
    • Journal Title

      Gastroenterology 134

      Pages: 1180-1190

    • NAID

      40016346603

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glycyrrhizin and its metabolite inhibit Smad3-mediated type I collagen gene transcription and suppress experimental murine liver fibrosis.2008

    • Author(s)
      Tadashi Moro
    • Journal Title

      Life Sciences 83

      Pages: 531-539

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 肝線維化機序の解明で今何が問題になっているのか2008

    • Author(s)
      稲垣 豊
    • Journal Title

      肝胆膵 57

      Pages: 187-192

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Emerging insights into transforming growth factor-β Smad signal in hepatic fibrogenesis2007

    • Author(s)
      Inagaki Y, Okazaki I
    • Journal Title

      Gut 56

      Pages: 284-292

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow-derived cells express matrix metalloproteinases and contribute to regression of liver fibrosis in mice2007

    • Author(s)
      Higashiyama R, Inagaki Y, Hong YY, 他8名
    • Journal Title

      Hepatology 45

      Pages: 213-222

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow cells in the liver : diverse cells, diverse effects2007

    • Author(s)
      Inagaki Y, Higashiyama R, Watanabe T, 他1名
    • Journal Title

      Hepatology 46

      Pages: 604-606

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Treatment Strategy for liver fibrosis through recruitment and differentiation of bone marrow stem/progenitor cells2007

    • Author(s)
      Inagaki Y, Higashiyama R, Okazaki I
    • Journal Title

      Hepatol Res 37

      Pages: 991-993

    • NAID

      10019796168

    • Related Report
      2008 Final Research Report
  • [Journal Article] Targeted and regulable expression of transgenes in hepatic stellate cells and myofibroblasts in culture and in vivo using an adenoviral Cre-LoxP system to antagonise hepatic fibrosis2007

    • Author(s)
      Kinoshita K, Iimuro Y, Inagaki Y, 他8名
    • Journal Title

      Gut 56

      Pages: 396-404

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats2007

    • Author(s)
      Kinoshita K, Iimuro Y, Inagaki Y, 他6名
    • Journal Title

      Gut 56

      Pages: 706-714

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Emerging insights into transforming growth factor-β Smad signal in hepatic fibrogenesis2007

    • Author(s)
      Yutaka Inagaki
    • Journal Title

      Gut 56

      Pages: 284-292

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow-derived cells express matrix metalloproteinases and contribute to regression of live fibrosis in mice2007

    • Author(s)
      Reiichi Higashiyama
    • Journal Title

      Hepatology 45

      Pages: 213-222

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeted and regulable expression of transgenes in hepatic stellate cells and myofibroblasts in culture and in vivo using an adenoviral Cre-LoxP system to antagonise hepatic fibrosis2007

    • Author(s)
      Kohji Kinoshita
    • Journal Title

      Gut 56

      Pages: 396-404

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats.2007

    • Author(s)
      Kohji Kinoshita
    • Journal Title

      Gut 56

      Pages: 706-714

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow cells in the liver: diverse cells, diverse effects (reply).2007

    • Author(s)
      Yutaka Inagaki
    • Journal Title

      Hepatology 46

      Pages: 604-606

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment Strategy for liver fibrosis through recruitment and differentiation of bone marrow stem/progenitor cells.2007

    • Author(s)
      Yutaka Inagaki
    • Journal Title

      Hepatol Res 37

      Pages: 991-993

    • NAID

      10019796168

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 骨髄細胞由来Matrix metalloproteinases (MMPs) による肝線維化改善機序の解明2008

    • Author(s)
      東山礼一、他
    • Organizer
      第22回肝類洞壁細胞研究会、ワークショップ2「肝再生と肝類洞壁細胞」
    • Place of Presentation
      久留米
    • Year and Date
      2008-11-29
    • Related Report
      2008 Final Research Report
  • [Presentation] 骨髄細胞由来Matrix metalloproteinases (MMPs)による肝線維化改善機序の解明.2008

    • Author(s)
      東山礼一
    • Organizer
      第22回肝類洞壁細胞研究会、ワークショップ2「肝再生と肝類洞壁細胞」
    • Place of Presentation
      久留米
    • Year and Date
      2008-11-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] Little contribution of bone marrow-derived cells to collagen production during hepatic fibrogenesis in mice2008

    • Author(s)
      Inagaki Y, et.al
    • Organizer
      59th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      San Francisco, CA
    • Year and Date
      2008-11-03
    • Related Report
      2008 Final Research Report
  • [Presentation] Matrix metallo-proteinases enhance migration of bone marrow-derived cells and contribute to the regression of experimental liver fibrosis2008

    • Author(s)
      Higashiyama R, et.al
    • Organizer
      59th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      San Francisco, CA
    • Year and Date
      2008-11-03
    • Related Report
      2008 Final Research Report
  • [Presentation] Little contribution of bone marrow-derived cells to collagen production during hepatic fibrogenesis in mice.2008

    • Author(s)
      Yutaka Inagaki
    • Organizer
      59th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      San Francisco, CA
    • Year and Date
      2008-11-03
    • Related Report
      2008 Annual Research Report
  • [Presentation] Matrix metalloproteinases enhance migration of bone marrow-derived cells and contribute to the regression of experimental liver fibrosis.2008

    • Author(s)
      Reiichi Higashiyama
    • Organizer
      59th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      San Francisco, CA
    • Year and Date
      2008-11-03
    • Related Report
      2008 Annual Research Report
  • [Presentation] 線維化治療と再生医学との接点2008

    • Author(s)
      稲垣豊
    • Organizer
      第32回ヒューマンサイエンス総合研究セミナー「NASHへの挑戦-創薬の可能性を探る-」
    • Place of Presentation
      東京
    • Year and Date
      2008-10-07
    • Related Report
      2008 Final Research Report
  • [Presentation] 線維化治療と再生医学との接点.2008

    • Author(s)
      稲垣 豊
    • Organizer
      第32回ヒューマンサイエンス総合研究セミナー「NASHへの挑戦一創薬の可能性を探る-」
    • Place of Presentation
      東京
    • Year and Date
      2008-10-07
    • Related Report
      2008 Annual Research Report
  • [Presentation] 臓器線維症の病態と治療戦略2008

    • Author(s)
      稲垣豊
    • Organizer
      第49回日本組織細胞化学会総会学術集会、シンポジウム(2)「線維化機構の分子形態的解析」
    • Place of Presentation
      長崎
    • Year and Date
      2008-10-05
    • Related Report
      2008 Final Research Report
  • [Presentation] 臓器線維症の病態と治療戦略.2008

    • Author(s)
      稲垣 豊
    • Organizer
      第49回日本組織細胞化学会総会学術集会、シンポジウム(2)「線維化機構の分子形態的解析」
    • Place of Presentation
      長崎
    • Year and Date
      2008-10-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] マウス非アルコール性脂肪性肝炎(NASH)モデルにおける分枝鎖アミノ酸(BCAA)の有用性の検討2008

    • Author(s)
      根本朋幸、他
    • Organizer
      第50回日本消化器病学会大会
    • Place of Presentation
      東京
    • Year and Date
      2008-10-02
    • Related Report
      2008 Final Research Report
  • [Presentation] マウス非アルコール性脂肪性肝炎(NASH)モデルにおける分枝鎖アミノ酸(BCAA)の有用性の検討.2008

    • Author(s)
      根本 朋幸
    • Organizer
      第50回日本消化器病学会大会
    • Place of Presentation
      東京
    • Year and Date
      2008-10-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] 骨髄由来細胞は肝線維化の進展に関与するか2008

    • Author(s)
      稲垣豊、他
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      松山
    • Year and Date
      2008-06-06
    • Related Report
      2008 Final Research Report
  • [Presentation] 骨髄由来細胞の動員とMatrix metalloproteinases (MMPs)発現による肝線維化改善機序の解明2008

    • Author(s)
      東山礼一、他
    • Organizer
      第44回日本肝臓学会総会、ワークショップ(8)「肝障害と修復に関する研究の展開」
    • Place of Presentation
      松山
    • Year and Date
      2008-06-06
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 骨髄由来細胞は肝線維化の進展に関与するか.2008

    • Author(s)
      稲垣 豊
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      松山
    • Year and Date
      2008-06-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] 皮膚創傷治癒ならびに線維化過程における骨髄由来細胞のコラーゲン合成への関与2008

    • Author(s)
      東山礼一、他
    • Organizer
      第40回日本結合組織学会学術大会・第55回マトリックス研究会大会合同学術集会
    • Place of Presentation
      東京
    • Year and Date
      2008-05-30
    • Related Report
      2008 Final Research Report
  • [Presentation] 皮膚創傷治癒ならびに線維化過程における骨髄由来細胞のコラーゲン合成への関与.2008

    • Author(s)
      東山礼一
    • Organizer
      第40回日本結合組織学会学術大会・第55回マトリックス研究会大会合同学術集会
    • Place of Presentation
      東京
    • Year and Date
      2008-05-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] マウス部分胆管結紮モデルの確立と抗線維化薬の薬効評価への応用2008

    • Author(s)
      茂呂忠、他
    • Organizer
      第40回日本結合組織学会学術大会・第55回マトリックス研究会大会合同学術集会
    • Place of Presentation
      東京
    • Year and Date
      2008-05-29
    • Related Report
      2008 Final Research Report
  • [Presentation] マウス部分胆管結紫モデルの確立と抗線維化薬の薬効評価への応用.2008

    • Author(s)
      茂呂 忠
    • Organizer
      第40回日本結合組織学会学術大会・第55回マトリックス研究会大会合同学術集会
    • Place of Presentation
      東京
    • Year and Date
      2008-05-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] 骨髄由来細胞は肝線維化の進展に関与するか2007

    • Author(s)
      稲垣豊、他
    • Organizer
      第21回肝類洞壁細胞研究会
    • Place of Presentation
      松山
    • Year and Date
      2007-12-22
    • Related Report
      2008 Final Research Report
  • [Presentation] 骨髄由来細胞は肝線維化の進展に関与するか.2007

    • Author(s)
      稲垣 豊
    • Organizer
      第21回肝類洞壁細胞研究会
    • Place of Presentation
      松山
    • Year and Date
      2007-12-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] Hepatocyte growth factor suppresses collagen gene transcription via nuclear export of Smad3 with galectin-72007

    • Author(s)
      Inagaki Y, et.al
    • Organizer
      58th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston, MA
    • Year and Date
      2007-11-05
    • Related Report
      2008 Final Research Report
  • [Presentation] Hepatocyte growth factor suppresses collagen gene transcription via nuclear export of Smad3 with galectin-7.2007

    • Author(s)
      Yutaka Inagaki
    • Organizer
      58th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston,MA
    • Year and Date
      2007-11-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] Transgenic dual reporter mouseを用いたコラーゲン合成と分解の包括的解析2007

    • Author(s)
      稲垣豊、他
    • Organizer
      第43回日本肝臓学会総会、ワークショップ(11)「肝線維化研究の進歩歩」
    • Place of Presentation
      東京
    • Year and Date
      2007-06-01
    • Related Report
      2008 Final Research Report
  • [Presentation] Transgenic dual reporter mouseを用いたコラーゲン合成と分解の包括的解析.2007

    • Author(s)
      稲垣 豊
    • Organizer
      第43回日本肝臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-06-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] Transgenic dual reporterマウスを用いたコラーゲン合成系および分解系の包括的解析2007

    • Author(s)
      茂呂忠、他
    • Organizer
      第39回日本結合組織学会学術大会・第54回マトリックス研究会大会合同学術集会
    • Place of Presentation
      東京
    • Year and Date
      2007-05-11
    • Related Report
      2008 Final Research Report
  • [Presentation] ブレオマイシン誘導皮膚硬化症における骨髄由来細胞の関与2007

    • Author(s)
      東山礼一、他
    • Organizer
      第39回日本結合組織学会学術大会・第54回マトリックス研究会大会合同学術集会
    • Place of Presentation
      東京
    • Year and Date
      2007-05-11
    • Related Report
      2008 Final Research Report
  • [Presentation] Transgenic dual reporterマウスを用いたコラーゲン合成系および分解系の包括的解析2007

    • Author(s)
      茂呂 忠
    • Organizer
      第39回日本結合組織学会学術大会・第54回マトリックス研究会大会 合同学術集会
    • Place of Presentation
      東京
    • Year and Date
      2007-05-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] ブレオマイシン誘導皮膚硬化症における骨髄由来細胞の関与.2007

    • Author(s)
      東山 礼一
    • Organizer
      第39回日本結合組織学会学術大会・第54回マトリックス研究会大会 合同学術集会
    • Place of Presentation
      東京
    • Year and Date
      2007-05-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] 臓器線維症の進展ならびに改善における骨髄と末梢の臓器相関2007

    • Author(s)
      稲垣豊、他
    • Organizer
      第39回日本結合組織学会学術大会・第54回マトリックス研究会大会合同学術集会、シンポジウム(2)「結合組織疾患における最近のトピックス」
    • Place of Presentation
      東京
    • Year and Date
      2007-05-10
    • Related Report
      2008 Final Research Report
  • [Presentation] 臓器線維症の進展ならびに改善における骨髄と末梢の臓器相関.2007

    • Author(s)
      稲垣 豊
    • Organizer
      第39回日本結合組織学会学術大会・第54回マトリックス研究会大会 合同学術集会
    • Place of Presentation
      東京
    • Year and Date
      2007-05-10
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://health.med.u-tokai.ac.jp/staff/inagaki/paper.html

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://health.med.u-tokai.ac.jp/staff/inagaki/paper.html

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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