A basic research of steatoic liver transplantation from a view of PAR-1 activity in the hepatic sinusoid

• Project/Area Number: 23791524
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Mie University
• Principal Investigator: HAMADA TAKASHI 三重大学, 医学(系)研究科(研究院), リサーチアソシエイト (50542164)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 肝臓移植 / 類洞 / 脂肪肝 / 虚血再灌流障害 / 肝虚血再還流障害 / 肝虚血再灌流障害

Research Abstract

Hepatic steatosis remains a problem in liver transplantation, which often result in graft failure after transplantation. This problem makes a limitation of the increase of healthy donor pool. In this present research using rat steatotic liver transplantation models, we clarified that Proteinase activated receptor (PAR)-1, a receptor that regulates inflammation as well as thrombin-associated coagulation, is highly expressed in the fatty livers, which results in early graft loss. This graft loss is associated with increased hepatic apoptosis and impaired liver regengeration, as well as inadequate coagulation in the hepatic sinusoid. In addition, such an early graft failure was improved by using PAR-1 antagonist, which is promising an expansion of donor pooling in liver transplantation in the future.

Research Products

• [Journal Article] Dual cytoprotective effects of splenectomy for small-for-size liver transplantation in rats (2012)
  • Author(s): Kuriyama N, Isaji S,Kishiwada M, Ohsawa I,Hamada T, Mizuno M, Usui M, Sakurai H, Tabata M,Yamada T.
  • Journal Title: Liver transplantation Volume: Vol 18 (11)
  • Peer Reviewed
• [Presentation] Increased proteinase activated receptor(PAR)-1 expression and metalloproteinase(MMP)-9 positive leukocyte migration aggravates liver damage in steatosis during hepatic ischemia and reperfusion injury (2011)
  • Author(s): Hamada T, Kato H, Magawa S, Ohsawa I, Kishiwada M, Mizuno S, Usui M, Sakurai H, Tabata M, Isaji S.
  • Organizer: American Transplant congress 2011
  • Place of Presentation: 米国フィラデルフィア
• [Presentation] Increased proteinase activated receptor(PAR)-1 expression and MMP-9 positive leukocyte migration aggravates liver damage in steatosis during hepatic ischemia and reperfusion injury (2011)
  • Author(s): 濱田 賢司
  • Organizer: アメリカ移植学会
  • Place of Presentation: アメリカ合衆国フィラデルフィア