Identification of hepatic encephalopathy induced proteins using by a bio-artificial liver and toxin receptor knock out hepatitis model mice

• Project/Area Number: 21590862
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: MATSUURA Tomokazu 東京慈恵会医科大学, 医学部, 准教授 (30199749)
• Co-Investigator(Renkei-kenkyūsha): KIMURA Naofumi 東京慈恵会医科大学, 医学部, 教授 (80138742)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 肝臓学 / 肝性脳症 / バイオ人工肝臓 / 肝炎モデルマウス / 肝炎モデル / マウス / ジフテリア毒素

Research Abstract

Identification of unknown hepatic encephalopathy induced substances to cause the "rapid cerebral edema" in fulminant hepatitis is required in development of the treatment and diagnosis of fatal hepatic encephalopathy. The main purpose of this study is identification of brain astrocytes damage inducing plasma proteins. A candidate of fatal hepatic encephalopathy inducing proteins, temporary named protein A, was able to identify by proteomic analysis. Protein A induced the cytotoxicity to cultured astrocytes. Hepatic encephalopathy was induced in the TRECK hepatitis model mice. In addition, we could observe diffuse astrocyte swelling in acute hepatic encephalopathy by DWI on MRI, as a decrease in the ADC. We will study whether protein A induce hepatic encephalopathy in vivo model and clinical cases in next step, and promote the treatment for fatal encephalopathy.

Research Products

• [Journal Article] Transplantation of liver organoids in the omentum and kidney (2011)
  • Author(s): Saito R、Ishii Y、Ito R、Nagatsuma K、Tanaka K、Saito M、Maehashi H、Nomoto H、Ohkawa K、Mano H、Aizawa M、Hano H、Yanaga K、Matsuura T
  • Journal Title: Artif Organs Volume: Vol.35, No.1 Issue: 1 Pages: 80-83
  • DOI: 10.1111/j.1525-1594.2010.01049.x
  • Peer Reviewed
• [Journal Article] Transplantation of liver organoids in the omentum and kidney. (2011)
  • Author(s): alto R, Ishii Y, Ito R, Nagatsuma K, Tanaka K, Saito M, Maehashi H, Nomoto H, Ohkawa K, Mano M, Aizawa M, Hano H, Yanaga K, Matsuura T.
  • Journal Title: Artif Organs. Volume: 35 Pages: 80-83
  • Peer Reviewed
• [Journal Article] Transplantation of liver organoids in the omentum and kidney (2011)
  • Author(s): Saito R, Ishii Y, Ito R, Nagatsuma K, Tanaka K, Saito M, Mehashi H, Matsuura T, et al.
  • Journal Title: Artif Organs (in press)
  • Peer Reviewed
• [Journal Article] ^<13> Cグルコース呼気試験を利用した3次元還流培養系の活性測定とその応用 (2010)
  • Author(s): 田中賢、松浦知和、中田浩二
  • Journal Title: Radioisotope Volume: Vol.59, No.7 Pages: 435-440
  • NAID: 10026799885
• [Journal Article] ^<13>Cグルコース呼気試験を利用した3次元還流培養系の活性測定とその応用 (2010)
  • Author(s): 田中賢、松浦知和、中田浩二
  • Journal Title: Radioisotopes Volume: 59 Pages: 435-440
  • NAID: 10026799885
• [Journal Article] Three-dimensional culture using a radial flow bioreactor induces matrix metalloprotease 7-mediated EMT-like process in tumor cells via TGFβ1/Smad pathway (2009)
  • Author(s): Shibata S, Marushima H, Asakura T, Matsuura T, Eda H, Aoki K, Matsudaira H, Ueda K, Ohkawa K
  • Journal Title: Int J Oncol Volume: Vol.34, No.5 Pages: 1433-1448
  • Peer Reviewed
• [Journal Article] Three-dimensuonal culture using a radialflow bioreactor induces matrix metalloprotease 7-mediated EMT-like process in tumor cells via TGFβ1/Smad pathway. (2009)
  • Author(s): Shibata S, Marushima H, Asakura T, Matsuura T, Eda H, Aoki K, et al.
  • Journal Title: Int J Oncol 34 Pages: 1433-1448
  • Peer Reviewed
• [Presentation] (ワークショップ)肝再生医学臨床応用を目指した研究の新展開類洞類似構造を再現した肝臓オルガノイドの作製 (2010)
  • Author(s): 松浦知和、石井雄二、相澤守
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-28
• [Presentation] (ワークショップ)肝再生医学 臨床応用を目指した研究の新展開、類洞類似構造を再現した肝臓オルガノイドの作製 (2010)
  • Author(s): 松浦知和, 石井雄二, 相澤守
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形市
  • Year and Date: 2010-05-28
• [Book] バイオリアクターシステム (2009)
  • Author(s): 松浦知和, 他
  • Publisher: シーエムシー出版
• [Patent(Industrial Property Rights)] ガス混合装置及びガス混合方法 (2011)
  • Inventor(s): 藤原邦彦、松浦知和
  • Industrial Property Rights Holder: エイブル(株)、松浦知和、大川清
  • Acquisition Date: 2011-11-25
• [Patent(Industrial Property Rights)] バイオリアクター (2010)
  • Inventor(s): 相澤守、松浦知和
  • Industrial Property Rights Holder: 学校法人明治大学
  • Acquisition Date: 2010-11-26