Roles of AGEs as exacerbation factor in pathogenesis of tissue remodeling and the development of novel targeted therapy

• Project/Area Number: 15K08605
• 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): 豊村 隆男 就実大学, 薬学部, 講師 (40425137) ; 渡邊 政博 就実大学, 薬学部, 助教 (10758246)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 炎症 / 組織リモデリング / サイトカイン / 分子標的

Outline of Final Research Achievements

We screened the binding factor which can interact with HMGB1 by ProtoArray analysis, and studied the pathophysiological roles of its interaction. As the result, we found that TWEAK can interact with HMGB1 with high affinity. TWEAK induced the enhancement of IL-8 mRNA expression in endothelial cells. AGEs specifically bind to TWEAK, and inhibited some inflammatory activities including TWEAK-induced IL-8 mRNA expression. These findings indicated the importance of TWEAK-AGEs interaction as novel therapeutic target molecule in the inflammatory diseases.

Research Products

• [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
  • 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
  • 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 response (2017)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] AGEs-RAGE間相互作用に影響を与える生理活性因子の同定と性状 (2017)
  • Author(s): 森 秀治 他
  • Organizer: ConBio2017（第90回日本分子生物学会，第90回日本生化学会合同大会）
• [Presentation] 破骨細胞分化抑制因子としてのSHIL004の機能解析 (2017)
  • Author(s): 豊村隆男 他
  • Organizer: ConBio2017（第90回日本分子生物学会，第90回日本生化学会合同大会）
• [Presentation] ゲノム編集によるAGEsの作用メカニズム解析プラットフォームの構築 (2017)
  • Author(s): 渡邊政博 他
  • Organizer: 第132回日本薬理学会近畿部会
• [Presentation] 非炎症分子SHILsはサイトカインとともに破骨細胞分化を調節する (2016)
  • Author(s): 豊村隆男 他
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2016-12-02
• [Presentation] AGEsによるTNF関連分子の機能変化 (2016)
  • Author(s): 渡邊政博 他
  • Organizer: 第130回日本薬理学会近畿部会
  • Place of Presentation: 京都大学百周年時計台記念館（京都市）
  • Year and Date: 2016-11-19
• [Presentation] AGEs親和性因子としての60S ribosomal proteinの単離 (2016)
  • Author(s): 森 秀治 他
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（仙台市）
  • Year and Date: 2016-09-26
• [Presentation] 破骨細胞分化ステージ特異的な非炎症性物質SHIL001及びSHIL002の効果 (2015)
  • Author(s): 豊村隆男
  • Organizer: 第38回日本分子生物学会・第88回日本生化学会合同大会
  • Place of Presentation: 神戸国際会議場（神戸市）
  • Year and Date: 2015-12-02
• [Presentation] AGEs-RAGE結合増大活性を示すHMGB1結合因子の探索 (2015)
  • Author(s): 森 秀治
  • Organizer: 第38回日本分子生物学会・第88回日本生化学会合同大会
  • Place of Presentation: 神戸国際会議場（神戸市）
  • Year and Date: 2015-12-01
• [Presentation] HMGB1と相互作用するサイトカインに対するAGEsの影響 (2015)
  • Author(s): 渡邊政博
  • Organizer: 第38回日本分子生物学会・第88回日本生化学会合同大会
  • Place of Presentation: 神戸国際会議場（神戸市）
  • Year and Date: 2015-12-01