Protecting liver sinusoidal endothelial cells suppresses apoptosis in acute liver damage

• Project/Area Number: 15K19870
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: University of Tsukuba
• Principal Investigator: TAMURA Takafumi 筑波大学, 医学医療系, 研究員 (20633192)
• 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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Drug Delivery System / 肝類洞内皮細胞 / 肝細胞 / アポトーシス / SiRNA, Bax / DDS / SiRNA / Apoptosis / Bax / MEND

Outline of Final Research Achievements

Bax siRNA was transfected into a sinusoidal endothelial cell line (M1) to suppress apoptosis. C57BL/6J mice were divided into three groups: (i) a control group, only intravenous saline; (ii) a nonselective group, injections of siRNA sealed in the nonselective DDS; and (iii) an LSEC-transfer efficient group, injections of siRNA sealed in an LSEC-transfer efficient
DDS. Bax siRNA had an anti-apoptotic effect on M1 cells. Silver impregnation staining indicated that the sinusoidal space was maintained in the LSEC-transfer efficient group but not in the other groups. Electron microscopy showed that the LSECs were slightly impaired, although the sinusoidal structure was maintained in the LSEC-transfer efficient group. Hepatocyte apoptosis was reduced by the efficient suppression of LSEC apoptosis with a novel DDS. Protecting the sinusoidal structure by suppressing LSEC damage will be an effective treatment for acute liver failure.

Research Products

• [Journal Article] Protecting liver sinusoidal endothelial cells suppresses apoptosis in acute liver damage. (2016)
  • Author(s): Tanoi T, Tamura T, Sano N, Nakayama K, Fukunaga K, Zheng YW, Akhter A, Sakurai Y, Hayashi Y, Harashima H, Ohkohchi N.
  • Journal Title: Hepatol Res Volume: 未定 Issue: 7 Pages: 697-706
  • DOI: 10.1111/hepr.12607
  • NAID: 120007129460
  • Peer Reviewed / Open Access
• [Presentation] 肝類洞内皮細胞選択的アポトーシス抑制による急性肝障害治療の検討 (2015)
  • Author(s): 田野井智倫, 田村孝史, 佐野直樹, 中山 健, Afsana Akhter, 櫻井 遊, 林 泰弘, 原島秀吉, 大河内信弘
  • Organizer: 第70回 消化器外科学会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2015-07-15
• [Presentation] 新規Drug Dwlivery System を用いた肝類洞内皮細胞のアポトーシス抑制の急性肝障害における効果の検討 (2015)
  • Author(s): 田野井智倫,田村孝史,佐野直樹,中山 健,福永 潔,村田聡一郎,Akhter A,櫻井 遊,林 泰弘,原島秀吉,大河内信弘
  • Organizer: 第11回広島肝臓プロジェクト研究センターシンポジウム
  • Place of Presentation: ホテルグランヴィア広島（広島県広島市）
  • Year and Date: 2015-07-04