Treatment for fulminant hepatitis focusing on soluble receptor for HMGB1 (sRAGE)

• Project/Area Number: 26430093
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Keio University
• Principal Investigator: Shinoda Masahiro 慶應義塾大学, 医学部(信濃町), 准教授 (50286499)
• Co-Investigator(Kenkyū-buntansha): 雨宮 隆介 慶應義塾大学, 医学部(信濃町), 助教 (60626696) ; 高柳 淳 慶應義塾大学, 医学部(信濃町), 共同研究員 (80245464)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 急性肝不全 / HMGB1 / 可溶性受容体 / RAGE / 遺伝子導入 / sRAGE

Outline of Final Research Achievements

High-mobility group box 1 (HMGB1) has recently been identified as an important mediator of various kinds of acute and chronic inflammation. Acute liver failure is a lethal disease. We constructed plasmid encoding cDNA for sRAGE and performed in vitro and in vivo experiments to test if the plasmid works for acute liver failure. Western blot analysis showed enhanced expressions of sRAGE protein in HeLa cells transfected with plasmid. The culture supernatant of HeLa cells transfected with the plasmid inhibited TNF production from macrophages. Transfected rats showed tendency of decreased hepatic enzymes, It is possible that sRAGE is effective for the treatment for acute liver failure.

Research Products

• [Presentation] HMGB1 targeting therapy for acute liver failure. (2016)
  • Author(s): 篠田昌宏、溝田高聖, 雨宮隆介, 西山亮, 高柳淳, 島田薫, 海老沼浩利, 尾原秀明, 板野理, 北川雄光
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: アスティ徳島（徳島県徳島市）
  • Year and Date: 2016-07-14
• [Presentation] ブタ急性肝不全モデルにおけるHMGB1吸着療法の試み (2014)
  • Author(s): 雨宮隆介, 篠田昌宏, 西山亮, 大島剛, 高野公徳, 井上武大, 島田薫, 山田晋吾, 宮庄拓, 北郷実, 尾原秀明, 竹内裕也, 板野理, 丸山征郎, 北川雄光
  • Organizer: 第21回外科侵襲とサイトカイン研究会
  • Place of Presentation: 徳島大学藤井節郎記念医科学センター（徳島県・徳島市）
  • Year and Date: 2014-12-13