Development of new reagent for liver diseases using S1P and hyaluronic acid

• Project/Area Number: 23390319
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: University of Tsukuba
• Principal Investigator: OHKOHCHI NOBUHIRO 筑波大学, 医学医療系, 教授 (40213673)
• Co-Investigator(Kenkyū-buntansha): FUKUNAGA Kiyoshi 筑波大学, 医学医療系, 講師 (20361339) ; TAMURA Tamura 筑波大学, 医学医療系, 講師 (20633192) ; KOBAYASHI Akihiko 筑波大学, 医学医療系, 講師 (10446552)
• Co-Investigator(Renkei-kenkyūsha): MURATA Soichiro 筑波大学, 医学医療系, 准教授 (40436275)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
• Keywords: 肝再生 / 血小板 / 線維化抑制 / 肝硬変 / S1P / ヒアルロン酸

Research Abstract

We previously reported that platelets have ability of liver regeneration and liver protection. Sphingosine 1 phosphate (S1P) is the main component of this ability. In this study, we revealed that S1P directly activates liver sinusoidal endothelial cells. In addition, we generated new drug delivery system (DDS) using hyaluronic acid (HA) which is selectively incorporated into liver sinusoidal endothelial cells. The new reagent by adapting S1P and HA ameliorated rat ischemia-reperfusion injury of the liver.

Research Products

• [Journal Article] Role of platelets in chr onic liver disease and acute liver injury (2014)
  • Author(s): Nowatari T, Murata S, Fukunaga K, O hkohchi N
  • Journal Title: Hepatol Res Volume: 44(2) Issue: 2 Pages: 165-72
  • DOI: 10.1111/hepr.12205
  • Peer Reviewed
• [Journal Article] Signal tran sduction of platelet-induced liver regeneration and decrease of liver fibrosis (2014)
  • Author(s): Murata S, Maruyama T, Nowatari T, T akahashi K, Ohkohchi N
  • Journal Title: Int J Mol Sci Volume: 15(4) Issue: 4 Pages: 5412-25
  • DOI: 10.3390/ijms15045412
  • Peer Reviewed
• [Journal Article] Protective effect of heme oxygenase-1 on hepatic isch emia-reperfusion injury through inh ibition of platelet adhesion to the sinusoids (2013)
  • Author(s): Tamura T, Kondo T, Ogawa K, Fukunag a K, Ohkohchi N
  • Journal Title: J Surg Res Volume: 180(1) Issue: 1 Pages: 62-72
  • DOI: 10.1016/j.jss.2012.11.030
  • Peer Reviewed
• [Journal Article] Effects of throm bopoietin on growth of hepatocellul ar carcinoma : Is thrombopoietin the rapy for liver disease safe or not? (2013)
  • Author(s): Nozaki R, Murata S, Nowatari T, Mar uyama T, Ikeda N, Kawasaki T, Fukun aga K, Ohkohchi N
  • Journal Title: Hepatol Res Volume: 43(6) Issue: 6 Pages: 610-20
  • DOI: 10.1111/hepr.12006
  • Peer Reviewed
• [Journal Article] Platelet transfusion improves liver function in patients with chronic liver disease and cirrhosis (2013)
  • Author(s): Maruyama T, Murata S, Takahashi K, Tamura T, Nozaki R, Ikeda N, Fukuna ga K, Oda T, Sasaki R, Ohkohchi N
  • Journal Title: Tohoku J Exp Med Volume: 229(3) Pages: 213-20
  • NAID: 10031161721
• [Journal Article] Platelet transfusion improves liver function in patients with chronic liver disease and cirrhosis. (2013)
  • Author(s): Maruyama T, Murata S, Takahashi K, Tamura T, Nozaki R, Ikeda N, Fukunaga K, Oda T, Sasaki R, Ohkohchi N.
  • Journal Title: Tohoku J Exp Med Volume: 229(3) Pages: 213-220
  • NAID: 10031161721
  • Peer Reviewed
• [Journal Article] Platelet transfusion improves liver function in patients with chronic liver disease and cirrhosis. (2013)
  • Author(s): Maruyama T
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 229(3) Pages: 213-220
  • Peer Reviewed
• [Journal Article] Regulation of signal transduction a nd role of platelets in liver regen eration (2012)
  • Author(s): Nowatari T, Fukunaga K, Ohkohchi N
  • Journal Title: Int J Hepatol Volume: - Pages: 542479-542479
  • DOI: 10.1155/2012/542479
  • Peer Reviewed
• [Journal Article] Platelet-derived adenosine 5' - triphosphate suppresses activa tion of human hepatic stellate cell - in vitro study - (2012)
  • Author(s): Ikeda N, Murata S, Maruyama T, Tamu ra T, Nozaki R, Kawasaki T, Fukunag a K, Oda T, Sasaki R, Homma M, Ohko hchi N
  • Journal Title: Hepatol Res Volume: 42(1) Pages: 91-102
• [Journal Article] Protective effect of heme oxygenase-1 on hepaticischemia-reperfusion injury throughinhibition of platelet adhesion to the sinusoids (2012)
  • Author(s): Tamura T, Kondo T, Ogawa K, Fukunaga K, Ohkohchi N.
  • Journal Title: J Gastroenterol Hepatol Volume: 28(4) Issue: 4 Pages: 700-6
  • DOI: 10.1111/jgh.12075
  • Peer Reviewed
• [Journal Article] Platelet-derived adenosine 5'-triphosphate suppresses activation of human hepatic stellate cell: In (2012)
  • Author(s): Ikeda N
  • Journal Title: Hepatology Research Volume: 42 Issue: 1 Pages: 91-102
  • DOI: 10.1111/j.1872-034x.2011.00893.x
  • Peer Reviewed
• [Presentation] スフィンゴシン 1 リン酸はヒト肝星細胞の増殖・活性化を抑制する-新しい肝線維か抑制療法の開発- (2014)
  • Author(s): 野渡剛之
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 国立京都国際会館, 京都
  • Year and Date: 2014-04-04
• [Presentation] Sinusoidal endothelial cells promote hepatocyte proliferation with S1P (2013)
  • Author(s): Murata S
  • Organizer: 17th International symposium on cells of the hepatic sinusoid
  • Place of Presentation: 大阪国際会議場, 大阪
  • Year and Date: 2013-09-24
• [Presentation] 血小板による肝再生メカニズムの解明と新規肝再生治療の可能性 (2013)
  • Author(s): 野渡剛之
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: マリンメッセ福岡, 福岡
  • Year and Date: 2013-04-11
• [Presentation] 血小板による肝再生メカニズムの解明と新規肝再生治療の可能性 (2013)
  • Author(s): 野渡剛之，佐野直樹，丸山岳人，高橋一広，野崎礼史，村田聡一郎，大河内信弘
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: マリンメッセ福岡
• [Presentation] Sinusoidal endothelial cells promote hepatocyte proliferation with S1P (2013)
  • Author(s): Murata S
  • Organizer: 17th International symposium on cells of the hepatic sinusoid
  • Place of Presentation: 大阪国際会議場
• [Presentation] 血小板による肝硬変に対する新規治療法の開発 (血小板野持つ抗線維化メカニズムの解明) (2012)
  • Author(s): 池田直哉
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 石川県立音楽堂, 金沢
  • Year and Date: 2012-06-07
• [Presentation] 血小板は Kupffer 細胞との相互作用により肝再生を促進する (2012)
  • Author(s): 高橋一広
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 幕張メッセ, 千葉
  • Year and Date: 2012-04-13
• [Presentation] 血小板はKupffer細胞との相互作用により肝再生を促進する (2012)
  • Author(s): 高橋一広
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 千葉
• [Presentation] 血小板による肝硬変に対する新規治療法の開発（血小板の持つ抗線維化メカニズムの解明） (2012)
  • Author(s): 池田直哉
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢
• [Patent(Industrial Property Rights)] スフィンゴシン 1 リン酸により修飾されたヒアルロン酸 (2014)
  • Inventor(s): 原島秀吉, 兵藤守, 鳥谷部尚之, 大河内信弘, 田村孝史, 佐野直樹
  • Industrial Property Rights Holder: 北海道大学, 筑波大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-043549
  • Filing Date: 2014-03-06