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Development of prophylaxis and therapy system for metabolic stmdorome by regulation of AIM function

Research Project

Project/Area Number 24390196
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

ARAI Satoko  東京大学, 医学(系)研究科(研究院), 准教授 (60422276)

Co-Investigator(Renkei-kenkyūsha) MIYAZAKI Toru  東京大学, 大学院医学系研究科, 教授 (30396270)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
KeywordsAIM / 生活習慣病 / HCC / メタボリックシンドローム / 慢性炎症
Outline of Final Research Achievements

Since AIM (apoptosis inhibitor of macrophage), a secreted protein produced from macrophages, has been shown to be involved in metabolic syndromes such as obesity, insulin resistance and atherosclerosis, regulation of both function and amount of AIM in body can be effective to prevent or control the AIM-related diseases. In this study, we investigated mechanism and materials for regulation of function and level of AIM. In addition, we presented that AIM is involved in the obesity-derived diseases such like auto-reactive antibody production and steatosis-derived hepatocellular carcinoma. Furthermore, we performed a large-scale analysis for blood AIM concentration in human including healthy individuals and patients with liver diseases, and demonstrated that AIM can be applied for the diagnosis of HCC in humans.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report

Research Products

(29 results)

All 2015 2014 2013 2012 Other

All Journal Article (15 results) (of which Peer Reviewed: 11 results,  Open Access: 6 results,  Acknowledgement Compliant: 5 results) Presentation (12 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] Tricking an ancient immune function to eradicate hepatocellular carcinoma2015

    • Author(s)
      Miyazaki T, Arai S
    • Journal Title

      Molecular and Cellular Oncology

      Volume: 2

    • DOI

      10.4161/23723556.2014.985915

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Circulating AIM Prevents Hepatocellular Carcinoma through Complement Activation2014

    • Author(s)
      Maehara N, Arai S, Mori M, Iwamura Y, Kurokawa J, Kai T, Kusunoki S, Taniguchi K, Ikeda K, Ohara O, Yamamura K, Miyazaki T
    • Journal Title

      Cell Report

      Volume: 9 Pages: 61-74

    • DOI

      10.1016/j.celrep.2014.08.058

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Circulating AIM as an Indicator of Liver Damage and Hepatocellular Carcinoma in Humans2014

    • Author(s)
      Yamazaki T, Mori M, Arai S, Tateishi R, Abe M, Ban M, Nishijima A, Maeda M, Asano T, Kai T, Izumino K, Takahashi J, Aoyama K, Harada S, Takebayashi T, Gunji T, Ohnishi S, Seto S, Yoshida Y, Hiasa Y, Koike K, Yamamura K, Inoue K, Miyazaki T
    • Journal Title

      Plos One

      Volume: 9

    • DOI

      10.1371/journal.pone.0109123

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Stabilization and Augmentation of Circulating AIM in Mice by Synthesized IgM-Fc2014

    • Author(s)
      Kai T, Yamazaki T, Arai S, Miyazaki T
    • Journal Title

      PLOS ONE

      Volume: 9

    • DOI

      10.1371/journal.pone.0097037

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression.2014

    • Author(s)
      Martinez VG, Escoda-Ferran C, Tadeu Simoes I, Arai S, Orta Mascaro M, Carreras E, Martinez-Florensa M, Yelamos J, Miyazaki T, Lozano F
    • Journal Title

      Cellular & Molecular Immunology

      Volume: Epub ahead of print Pages: 343-354

    • DOI

      10.1038/cmi.2014.12

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stabilization and augmentation of circulating AIM in mice by synthesized IgM-Fc.2014

    • Author(s)
      Kai T, Yamazaki T, Arai S, Miyazaki T
    • Journal Title

      PLOS ONE

      Volume: 未定

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MafB promotes atherosclerosis by inhibiting foam-cell apoptosis2014

    • Author(s)
      Hamada M, Nakamura M, Tran MT, Moriguchi T, Hong C, Ohsumi T, Dinh TT, Kusakabe M, Hattori M, Katsumata T, Arai S, Nakashima K, Kudo T, Kuroda E, Wu CH, Kao PH, Sakai M, Shimano H, Miyazaki T, Tontonz P, Takahashi S
    • Journal Title

      Nature Comminications

      Volume: 5 Pages: 1-14

    • DOI

      10.1038/ncomms4147

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Impacts of the apoptosis inhibitor of macrophage (AIM) on obesity-associated inflammatory diseases.2014

    • Author(s)
      Arai S, Miyazaki T
    • Journal Title

      Semin Immunopathol

      Volume: 36 Pages: 3-12

    • DOI

      10.1007/s00281-013-0405-5

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Obesity-associated autoantibody production requires AIM to retain IgM immune complex on follicular dendritic cells2013

    • Author(s)
      Arai, S., et al.
    • Journal Title

      Cell Report

      Volume: 3 Pages: 1187-1198

    • DOI

      10.1016/j.celrep.2013.03.006

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AIM : 炎症と生活習慣病を繋ぐ分子2013

    • Author(s)
      新井郷子
    • Journal Title

      Annual Review糖尿病・代謝・内分泌

      Pages: 99-105

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Apoptosis inhibitor of macrophage(AIM) diminishes lipid droplet-coating proteins leading to lipolysis in adipocytes2012

    • Author(s)
      Iwamura Y, Mori M, Nakashima K, Mikami T, Murayama K, Arai S, Miyazaki T.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 422 Pages: 476-481

    • DOI

      10.1016/j.bbrc.2012.05.018

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modification of N-glycosylation modulates the secretion and lipolytic function of Apoptosis Inhibitor of Macrophage (AIM).2012

    • Author(s)
      森真弓
    • Journal Title

      FEBS Letter

      Volume: 586 Pages: 3569-3574

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] マクロファージ由来因子AIMによる生活習慣病の病態制御2012

    • Author(s)
      新井郷子
    • Journal Title

      細胞工学

      Volume: 31 Pages: 1231-1236

    • Related Report
      2012 Annual Research Report
  • [Journal Article] アポトーシスと動脈硬化2012

    • Author(s)
      新井郷子
    • Journal Title

      動脈硬化予防

      Volume: 11 Pages: 36-41

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 肥満から慢性炎症、そして疾患へ-AIMによる慢性炎症誘発のメカニズム-2012

    • Author(s)
      新井郷子
    • Journal Title

      血管医学

      Volume: 13 Pages: 213-219

    • Related Report
      2012 Annual Research Report
  • [Presentation] Circulating AIM prevents hepatocellular carcinoma through complement activation2014

    • Author(s)
      新井郷子, 宮崎徹
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肝臓におけるAIMの補体活性化によるがん除去機構2014

    • Author(s)
      前原奈都美, 新井郷子, 森真弓, 宮崎徹
    • Organizer
      第37回分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒトにおける肝障害及び肝がんの指標としての血中AIM濃度2014

    • Author(s)
      山崎智子, 新井郷子, 宮崎徹
    • Organizer
      第37回分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Prevention of hepatocellular carcinoma by circulating AIM through complement activation2014

    • Author(s)
      Miyazaki T, Maehara N, Mori M, Arai S
    • Organizer
      Cell Symposium: Hallmark of Cancer
    • Place of Presentation
      Beijing, China
    • Year and Date
      2014-11-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] マクロファージ由来タンパク質AIMによる生体の新規恒常性維持機構2014

    • Author(s)
      新井郷子
    • Organizer
      第7回食品免疫学会次世代シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-06-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Obesity-associated autoantibody production requires AIM for retaining the immunecomplex on follicular dendritic cells2012

    • Author(s)
      新井郷子
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2012-12-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] Obesity-associated autoantibody production reauires AIM for retaining the immunecomplex on follicular dendritic cells2012

    • Author(s)
      新井郷子
    • Organizer
      EUROPEAN CONGRESS OF IMMUNOLOGY
    • Place of Presentation
      英国, グラスゴー
    • Year and Date
      2012-09-06
    • Related Report
      2012 Annual Research Report
  • [Presentation] A role for macrophage-derived AIM in humoral immune response and obesity-associated autoimmunity2012

    • Author(s)
      新井郷子
    • Organizer
      The 99th America Association of Immunology Annual Meeteing
    • Place of Presentation
      米国, ボストン
    • Year and Date
      2012-05-08
    • Related Report
      2012 Annual Research Report
  • [Presentation] Obesity-associated autoantibody production requires AIM to retain IgM immune complex on follicular dendritic cells.

    • Author(s)
      Arai S
    • Organizer
      Cell Symposia, Immunometabolism: from Mechanism to Therapy
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2013 Annual Research Report
  • [Presentation] Obesity-associated autoantibody production requires AIM to retain IgM immune complex on follicular dendritic cells.

    • Author(s)
      Arai S
    • Organizer
      The 3rd CSI/JSI/KAI Joint Symposium 2013
    • Place of Presentation
      Pohang, Korea
    • Related Report
      2013 Annual Research Report
  • [Presentation] Obesity-associated autoantibody production requires AIM to retain IgM immune complex on follicular dendritic cells

    • Author(s)
      Arai S, Honda S., Shibuya A., Li Q, Miyazaki T
    • Organizer
      2. 15th International Congress of Immunology
    • Place of Presentation
      Milan, Itay
    • Related Report
      2013 Annual Research Report
  • [Presentation] Obesity-associated autoantibody production requires AIM to retain IgM immune complex on follicular dendritic cells

    • Author(s)
      Arai S, Honda S., Shibuya A., Li Q, Miyazaki T
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張
    • Related Report
      2013 Annual Research Report
  • [Book] AIM: 炎症と生活習慣病を繋ぐ分子2013

    • Author(s)
      新井郷子, 宮崎徹
    • Total Pages
      7
    • Publisher
      中外医学社 Annual Review 糖尿病・代謝・内分泌2013
    • Related Report
      2013 Annual Research Report
  • [Book] マクロファージ由来タンパク質AIMの最新知見―その多様な機能と生活習慣病との関連性―2013

    • Author(s)
      新井郷子, 宮崎徹
    • Total Pages
      9
    • Publisher
      日本臨床
    • Related Report
      2013 Annual Research Report

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Published: 2012-04-23   Modified: 2019-07-29  

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