Regulation of liver repair via PGE receptor signaling

• Project/Area Number: 16K21350
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery; Digestive surgery
• Research Institution: Kitasato University
• Principal Investigator: Ohkubo Hirotoki 北里大学, 医学部, 助教 (50406930)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肝修復 / プロスタグランジン / 再潅流 / 再灌流 / プロスタグランディン / 再生医学 / 外科

Outline of Final Research Achievements

Impaired liver repair after liver surgery causes liver dysfunction, which is associated with a increased risk of morbidity and mortality. Here, we show that membranous prostaglandin synthase suppresses liver repair after liver injury in mice. mPGES-1 promotes accumulation of inflammatory macrophages, but not reparative macrophages, leading to delay in liver repair. Mice treated with the mPGES-1 inhibitor displayed increased liver protection and repair.

Research Products

• [Journal Article] Inhibition of microsomal prostaglandin E synthase-1 facilitates liver repair after hepatic injury in mice. (2018)
  • Author(s): Nishizawa N, Ito Y, Eshima K, Ohkubo H, Kojo K, Inoue T, Raouf J, Jakobsson PJ, Uematsu S, Akira S, Narumiya S, Watanabe M, Majima M.
  • Journal Title: J Hepatol. Volume: S0168-8278(18) Issue: 1 Pages: 30126-30130
  • DOI: 10.1016/j.jhep.2018.02.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Factors associated with a low initial cerebral oxygen saturation value in patients undergoing cardiac surgery (2017)
  • Author(s): Kobayashi Kensuke、Kitamura Tadashi、Kohira Satoshi、Torii Shinzo、Horai Tetsuya、Hirata Mitsuhiro、Mishima Toshiaki、Sughimoto Koichi、Ohkubo Hirotoki、Irisawa Yusuke、Matsushiro Takuya、Hayashi Hidenori、Miyata Yurie、Tsuchida Yuta、Ohtomo Naoki、Miyaji Kagami
  • Journal Title: Journal of Artificial Organs Volume: 20 Issue: 2 Pages: 110-116
  • DOI: 10.1007/s10047-016-0941-6
  • Peer Reviewed
• [Journal Article] BLT1 signalling protects the liver against acetaminophen hepatotoxicity by preventing excessive accumulation of hepatic neutrophils (2016)
  • Author(s): Kojo, K., Ito, Y., Eshima, K., Nishizawa, N., Ohkubo, H., Yokomizo, T., Shimizu, T., Watanabe, M.,Majima, M.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 29650-29650
  • DOI: 10.1038/srep29650
  • Peer Reviewed / Open Access
• [Presentation] PGE2 Derived from Microsomal Prostaglandin E Synthase-1 (Mpges-1) Induces Hepatic Ischemia/Reperfusion Injury through EP4 Receptor Signaling (2017)
  • Author(s): Nobuyuki Nishizawa, Yoshiya Ito, Ken Kojo, Hirotoki Ohkubo, Masahiko Watanabe, Masataka Majima.
  • Organizer: 40th ANNUAL CONFERENCE ON SHOCK
  • Int'l Joint Research
• [Presentation] 肝虚血再潅流障害後の肝修復過程におけるプロスタグランジンE2 の役割 (2017)
  • Author(s): 伊藤義也、西澤伸恭、大久保博世、古城憲、井上智仁、中本修治、大高史聖、都留世里、天野英樹、馬嶋正隆
  • Organizer: 第31 回肝類洞壁細胞研究会学術集会
• [Presentation] An inducible microsomal prostaglandin E syunthase-1 (mPGES-1) contributes to hepatic ischemia/reperfusion injury via PGE2/EP4 receptors. (2016)
  • Author(s): Ohkubo H, Ito Y, Nishizawa N, Inoue T, Kojo K, Amano H, Watanabe M, Majima M.
  • Organizer: The 8th Congress of International Federation of Shock Societies
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2016-10-03
  • Int'l Joint Research