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Research for homeodynamics regeneration-promoting drug discovery

Research Project

Project/Area Number 15K08253
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionKindai University

Principal Investigator

TAKAHASHI Hideo  近畿大学, 医学部, 教授 (60335627)

Co-Investigator(Kenkyū-buntansha) 劉 克約  岡山大学, 医歯薬学総合研究科, 非常勤研究員 (40432637)
西堀 正洋  岡山大学, 医歯薬学総合研究科, 教授 (50135943)
丹羽 淳子  近畿大学, 医学部, 講師 (60122082)
小堀 宅郎  近畿大学, 医学部, 助教 (60734697)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsホメオダイナミクス / 組織修復機構 / 血管内皮細胞 / HMGB1 / マクロファージ / マクローファージ分化 / 血管新生 / 骨髄ニッチ / マクロファージ分化
Outline of Final Research Achievements

Homeodynamics is one of the fundamental life phenomena in the fields of neurology, immunology, endocrinology, tissue repair and stem cells. During homeodynamics, the differentiation and activation of macrophages is involved in impairment of endothelium and angiogenesis. Damage-associated molecular patterns (DAMPs) are thought to play roles in the homeodynamics. Among DAMPs, interleukin(IL)-18 and advanced glycation end product(AGE) as well as high mobility group box protein1 (HMGB1) promote the differentiation and activation of macrophages.Especially, HMGB1, a ubiquitous chromatin component, is released by necrotic cells, apoptotic cells, and cells in profound distress. HMGB1 plays a critical role as a proinflammatory mediator. HMGB1 represents an important new target for drug development in a variety of inflammatory disorders, including stroke, brain injury, arteriosclerosis, and cancer.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (23 results)

All 2018 2017 2016 2015 Other

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 10 results,  Acknowledgement Compliant: 4 results) Presentation (9 results) (of which Invited: 1 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Interleukin-18 Amplifies Macrophage Polarization and Morphological Alteration, Leading to Excessive Angiogenesis.2018

    • Author(s)
      Kobori T, Hamasaki S, Kitaura A, Yamazaki Y, Nishinaka T, Niwa A, Nakao S, Wake H, Mori S, Yoshino T, Nishibori M, Takahashi H
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 334-334

    • DOI

      10.3389/fimmu.2018.00334

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phagocytosis of Advanced Glycation End Products (AGEs) in Macrophages Induces Cell Apoptosis.2017

    • Author(s)
      Gao Y, Wake H, Morioka Y, Liu K, Teshigawara K, Shibuya M, Zhou J, Mori S, Takahashi H, Nishibori M.
    • Journal Title

      Oxid Med Cell Longev.

      Volume: 2017:8419035 Issue: 1 Pages: 8419035-8419035

    • DOI

      10.1155/2017/8419035

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The specific localization of advanced glycation end-products (AGEs) in rat pancreatic islets.2017

    • Author(s)
      Morioka Y, Teshigawara K, Tomono Y, Wang D, Izushi Y, Wake H, Liu K, Takahashi HK, Mori S, Nishibori M.
    • Journal Title

      J Pharmacol Sci.

      Volume: 134(4) Issue: 4 Pages: 218-224

    • DOI

      10.1016/j.jphs.2017.07.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Advanced glycation end products attenuate the function of tumor necrosis factor-like weak inducer of apoptosis to regulate the inflammatory response2017

    • Author(s)
      Watanabe M, Toyomura T, Wake H, Liu K, Teshigawara K, Takahashi H, Nishibori M, Mori S
    • Journal Title

      Molecular and Cellular Biochemistry

      Volume: 印刷中 Issue: 1-2 Pages: 153-162

    • DOI

      10.1007/s11010-017-3045-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice.2017

    • Author(s)
      Fu L, Liu K, Wake H, Teshigawara K, Yoshino T, Takahashi H, Mori S, Nishibori M.
    • Journal Title

      Sci Rep.

      Volume: 7(1):1179. Issue: 1 Pages: 1179-1179

    • DOI

      10.1038/s41598-017-01325-y

    • NAID

      130007901378

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-high mobility group box-1 (HMGB1) antibody attenuates delayed cerebral vasospasm and brain injury after subarachnoid hemorrhage in rats2016

    • Author(s)
      Haruma J, Teshigawara K, Hishikawa T, Wang D, Liu K, Wake H, Mori S, Takahashi HK, Sugiu K, Date I, Nishibori M.
    • Journal Title

      Scientific reports

      Volume: 6 Issue: 1 Pages: 37755-37768

    • DOI

      10.1038/srep37755

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histidine-rich glycoprotein prevents septic lethality through regulation of immunothrombosis and inflammation.2016

    • Author(s)
      Wake H, Mori S, Liu K, Morioka Y, Teshigawara K, Sakaguchi M, Kuroda K, Gao Y, Takahashi H, Ohtsuka A, Yoshino T, Morimatsu H, Nishibori M.
    • Journal Title

      EBioMedicine

      Volume: 9 Pages: 180-194

    • DOI

      10.1016/j.ebiom.2016.06.003

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Soluble form of the receptor for advanced glycation end-products attenuates inflammatory pathogenesis in a rat model of lipopolysaccharide-induced lung injury.2016

    • Author(s)
      Izushi Y, Teshigawara K, Liu K, Wang D, Wake H, Takata K, Yoshino T, Takahashi HK, Mori S, Nishibori M.
    • Journal Title

      J Pharmacol Sci.

      Volume: S1347-8613(16)00026-8. Issue: 4 Pages: 1-9

    • DOI

      10.1016/j.jphs.2016.02.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-high mobility group box 1 monoclonal antibody improves ischemia/reperfusion injury and mode of liver regeneration after partial hepatectomy.2016

    • Author(s)
      Sugihara M, Sadamori H, Nishibori M, Sato Y, Tazawa H, Shinoura S, Umeda Y, Yoshida R, Nobuoka D, Utsumi M, Ohno K, Nagasaka T, Yoshino T, Takahashi HK, Yagi T, Fujiwara T.
    • Journal Title

      American Journal of Surgery

      Volume: 211 Issue: 1 Pages: 179-188

    • DOI

      10.1016/j.amjsurg.2015.06.025

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Voluntary exercise induces neurogenesis in the hypothalamus and ependymal lining of the third ventricle.2015

    • Author(s)
      Niwa A, Nishibori M, Hamasaki S, Kobori T, Liu K, Wake H, Mori S, Yoshino T, Takahashi H.
    • Journal Title

      Brain Structure & Function

      Volume: 印刷中 Issue: 3 Pages: 1863-2653

    • DOI

      10.1007/s00429-015-0995-x

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] マクロファージと血管内皮細胞の細胞間相互作用による血管新生促進機構の解析2018

    • Author(s)
      小堀 宅郎、濱﨑 真一、北浦 淳寛、山﨑 由衣、西中 崇、丹羽 淳子、西堀 正洋、髙橋 英夫
    • Organizer
      第138回日本薬理学会関東部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] SHRSPは赤血球産生の増加を示す2017

    • Author(s)
      西中 崇、丹羽淳子、小堀宅郞、髙橋英夫
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール、長崎新聞文化ホール
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] IL-18 はオステオポンチンを介してマクロファージ M2 分化と血管新生作用を増強する2017

    • Author(s)
      小堀 宅郎、濱崎 真一、北浦 淳寛、西中 崇、丹羽 淳子、森 秀治、西堀 正洋、髙橋 英夫
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール、長崎新聞文化ホール
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] 運動介入は骨髄微小環境を改善し血管系前駆細胞による脳卒中回復を促進する2017

    • Author(s)
      丹羽 淳子、西中 崇、小堀 宅郞、髙橋 英夫
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール、長崎新聞文化ホール
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] 終末糖化産物(AGEs)はマ クロファージによる血管内皮細胞の管腔形成を促進する2016

    • Author(s)
      濱﨑真一、小堀宅郎、北浦淳寛、丹羽淳子、髙橋 英夫
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      横浜パシフィコ(神奈川県)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] M2 マクロファージによる血管新生促進作用に対する IL-18 の影響2016

    • Author(s)
      小堀 宅郎、濱崎 真一、北浦 淳寛、加藤 貴史、丹羽 淳子、髙橋 英夫
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      横浜パシフィコ(神奈川県)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Tissue factor(TF)誘発DICモデルにおけるHistidine-rich glycoprotein(HRG)の動態及び治療効果について2015

    • Author(s)
      寺尾 欣也、 和氣 秀徳、 森岡 祐太、 勅使河原 匡、 劉 克約、 髙橋 英夫、 森 秀治、 西堀 正洋
    • Organizer
      第127回日本薬理学会近畿部会
    • Place of Presentation
      長良川国際会議場(岐阜県)
    • Year and Date
      2015-06-26
    • Related Report
      2015 Research-status Report
  • [Presentation] HMGB1 によるヒスタミン誘導性免疫応答調節効果2015

    • Author(s)
      加藤 貴史、岡 清正、髙橋 英夫、中村 敏一
    • Organizer
      第127回日本薬理学会近畿部会
    • Place of Presentation
      長良川国際会議場(岐阜県)
    • Year and Date
      2015-06-26
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] ホメオダイナミクス創薬~生体内恒常性維持機の活性化を目指して~2015

    • Author(s)
      髙橋 英夫
    • Organizer
      国立病院機構 福山医療センター オープンカンファレンス
    • Place of Presentation
      福山医療センター(広島県)
    • Year and Date
      2015-06-26
    • Related Report
      2015 Research-status Report
  • [Book] HMGB1とその受容体型研究の現状と展望2016

    • Author(s)
      高橋英夫、西堀正洋
    • Total Pages
      9
    • Publisher
      日本臨床
    • Related Report
      2016 Research-status Report
  • [Remarks] 近畿大学医学部薬理学教室

    • URL

      http://www.med.kindai.ac.jp/pharma/

    • Related Report
      2017 Annual Research Report 2015 Research-status Report
  • [Remarks] 近畿大学医学部薬理学教室

    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 好中球活性化に起因する疾患の治療薬、治療方法および検査方法2016

    • Inventor(s)
      西堀正洋、髙橋英夫、他
    • Industrial Property Rights Holder
      西堀正洋、髙橋英夫、他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-01-14
    • Acquisition Date
      2016-11-29
    • Related Report
      2016 Research-status Report
    • Overseas

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Published: 2015-04-16   Modified: 2020-01-20  

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