Role of CD39 on development of liver fibrosis and application of CD39 in treating liver fibrosis

• Project/Area Number: 15K19336
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Ehime University
• Principal Investigator: Yoshida Osamu 愛媛大学, 医学部附属病院, 講師 (70746809)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肝線維化 / 肝星細胞 / 細胞外ATP / CD39 / DAMP / ＣＤ３９

Outline of Final Research Achievements

Hepatic stellate cell (HSC) is involved in the pathogenesis of liver fibrosis, however the mechanism underlying HSC activation is not well known. Applicant have revealed that HSC expressed P2X7, the receptor for extracellular ATP (eATP) and HSC activation was mediated through ATP/P2X7 axis. Further, HSC activation was inhibited by CD39 which is a hydrolytic enzyme for eATP in vitro. Although therapeutic potential of CD39 in liver cirrhosis is still under investigation, CD39 may be a promising anti-fibrotic agent in liver diseases.

Research Products

• [Journal Article] Orthotopic mouse liver transplantation to study liver biology and allograft tolerance. (2016)
  • Author(s): Yokota S, Ueki S, Ono Y, Perez-Gutierrez A, Kimura S, Yoshida O, Murase N, Yasuda Y, Geller DA, Thomson AW
  • Journal Title: Nat Protc Volume: 11 Issue: 7 Pages: 1163-74
  • DOI: 10.1038/nprot.2016.073
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Liver transplantation in the mouse: Insights into liver immunobiology, tissue injury and allograft tolerance (2016)
  • Author(s): Yokota S, Yoshida O, Ono Y, Gellar DA, Thomson AW
  • Journal Title: Liver Transplantation Volume: 22 Issue: 4 Pages: 536-46
  • DOI: 10.1002/lt.24394
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 当科のPBCおけるGLOBE ScoreとUK-PBC Risk Scoreの有用性の検討当科のPBCおけるGLOBE ScoreとUK-PBC Risk Scoreの有用性の検討 (2016)
  • Author(s): 吉田理、阿部雅則、日浅陽一
  • Organizer: JDDW
  • Place of Presentation: 東京
  • Year and Date: 2016-11-03
• [Presentation] Promotion of liver transplant tolerance by liver plasmacytoid dendritic cells (2015)
  • Author(s): Yoshida O, Kimura S, Matta BM, Imai Y, Abe M, Hiasa Y, Thoson AW
  • Organizer: AASLD the Liver Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2015-11-13
  • Int'l Joint Research
• [Presentation] CD39による肝樹状細胞機能と肝虚血再灌流障害の制御 (2015)
  • Author(s): 吉田理、阿部雅則、日浅陽一
  • Organizer: 第51回 日本肝臓学会総会
  • Place of Presentation: 熊本市、熊本県
  • Year and Date: 2015-05-21