Pathophysiological role of AGEs as exacerbation factor in tissue remodeling and molecular targeted therapy

• Project/Area Number: 24590672
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Shujitsu University
• Principal Investigator: MORI Shuji 就実大学, 薬学部, 教授 (50220009)
• Co-Investigator(Kenkyū-buntansha): GOMITA Yutaka 就実大学, 薬学部, 元教授 (00088709) ; TOYOMURA Takao 就実大学, 薬学部, 助教 (40425137)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 組織リモデリング / 炎症 / 再生 / サイトカイン / 分子標的

Outline of Final Research Achievements

In this study, we isolated AGEs-binding factor of MW 70kDa by affinity chromatography from lung extract to elucidate the pathophysiological significance of AGEs in inflammatory sites, and to develop the novel targeted therapeutics. The binding between AGEs and RAGE was shown to be inhibited by AGEs-binding factor with dose-dependency, particularly by two different peptides in N-terminal region. These findings indicated the formation of functional complex in several inflammatory conditions.

Research Products

• [Journal Article] Histamine inhibits high mobility group box 1-induced adhesion molecule expression on human monocytes (2013)
  • Author(s): Takahashi H、Sadamori H、Teshigawara K、Niwa A、Liu K、Wake H、Mori S、Yoshino T、Nishibori M
  • Journal Title: Eur J Phamacol Volume: Vol.718、No.1-3 Issue: 1-3 Pages: 305-313
  • DOI: 10.1016/j.ejphar.2013.08.017
  • Peer Reviewed
• [Journal Article] Role of cell-cell interactions in high mobility group box 1 cytokine activity in human peripheral blood mononuclear cells and mouse splenocytes (2013)
  • Author(s): Kohka Takahashi H, Sadamori H, Liu K, Wake H, Mori S, Yoshino T, Yamamoto Y, Yamamoto H, Nishibori M
  • Journal Title: European Journal of Pharmacology Volume: 701(1-3) Issue: 1-3 Pages: 194-202
  • DOI: 10.1016/j.ejphar.2012.11.058
  • Peer Reviewed
• [Journal Article] Anti-high mobility group box-1 antibody therapy for traumatic brain injury (2012)
  • Author(s): Okuma Y, Liu K, Wake H, Zhang J, Maruo T, Date I, Yoshino T, Ohtsuka A, Otani N, Tomura S, Shima K, Yamamoto Y, Yamamoto H, Takahashi H K, Mori S, Nishibori M
  • Journal Title: Annals of Neurology Volume: 72 Issue: 3 Pages: 373-384
  • DOI: 10.1002/ana.23602
  • NAID: 130004427993
  • Peer Reviewed
• [Presentation] HMGB1結合因子の網羅的アレイ探索と機能調節 (2014)
  • Author(s): 森 秀治，和氣秀徳，劉克約，勅使川原匡，高橋英夫，西堀正洋，豊村隆男
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-11-25
• [Presentation] HMGB1結合因子によるAGEs-RAGE結合阻害解析 (2014)
  • Author(s): 森 秀治，和氣秀徳，劉克約，勅使川原匡，高橋英夫，西堀正洋，豊村隆男
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-10-16
• [Presentation] AGEs結合親和性に基づいたAGEs遮断ペプチドの同定 (2014)
  • Author(s): 横山隆太，豊村隆男，和氣秀徳，勅使川原匡，劉克約，高橋英夫，西堀正洋，森 秀治
  • Organizer: 第125回日本薬理学会近畿部会
  • Place of Presentation: 岡山コンベンションセンター（岡山）
  • Year and Date: 2014-06-20
• [Presentation] AGEs-RAGE相互作用に基づいた遮断物質探索系への応用
  • Author(s): 森 秀治
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Presentation] 70kD AGEs 結合因子によるAGEs- RAGE結合抑制作用
  • Author(s): 森 秀治
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場（神戸市）
• [Presentation] HMGB1，AGEs-RAGE系」に対する創薬プラットフォーム構築
  • Author(s): 森 秀治
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場（福岡市）
• [Presentation] 非炎症性物質の長期曝露に伴うマクロファージの炎症応答変化
  • Author(s): 豊村隆男
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場（福岡市）