Establish of novel therapy for DIC and multiple organ failures with apolipoprotein M

• Project/Area Number: 15K15378
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Kurano Makoto 東京大学, 医学部附属病院, 講師 (60621745)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 敗血症 / DIC / 多臓器不全 / アポ蛋白M / スフィンゴシン1－リン酸 / スフィンゴシン１－リン酸 / アポリポ蛋白M / スフィンゴシン1-リン酸 / 播種性血管内凝固症候群

Outline of Final Research Achievements

We found that the overexpression of apolipoprotein M (ApoM), an apolipoprotein carried on HDL, ameliorated the survival rate and organ injuries caused by the treatment with lipopolysaccharides, while the suppression of apoM deteriorated them. Moreover, we successfully improved the outcomes of the injection with lipopolysaccharides with recombinant apoM. These findings suggest that apoM can be applied to the treatment with DIC and/or multiple organ failure which occur consequently to sepsis.

Research Products

• [Journal Article] Involvement of CETP (Cholesteryl Ester Transfer Protein) in the Shift of Sphingosine-1-Phosphate Among Lipoproteins and in the Modulation of its Functions. (2017)
  • Author(s): Kurano, M., Hara, M., Ikeda, H., Tsukamoto, K., and Yatomi, Y
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 37 Pages: 506-514
  • DOI: 10.1161/atvbaha.116.308692
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Vehicle-dependent Effects of Sphingosine 1-phosphate on Plasminogen Activator Inhibitor-1 Expression (2017)
  • Author(s): Takahashi, C., Kurano, M., Nishikawa, M., Kano, K., Dohi, T., Miyauchi, K., Daida, H., Shimizu, T., Aoki, J., and Yatomi, Y.
  • Journal Title: J Atheroscler Thromb Volume: in press Issue: 9 Pages: 954-969
  • DOI: 10.5551/jat.37663
  • NAID: 130006038432
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increased mRNA levels of sphingosine kinases and S1P lyase and reduced levels of S1P were observed in hepatocellular carcinoma in association with poorer differentiation and earlier recurrence. (2016)
  • Author(s): Uranbileg B, Ikeda H, Kurano M, Enooku K, Sato M, Saigusa D, Aoki J, Ishizawa T, Hasegawa K, Kokudo N, Yatomi Y.
  • Journal Title: PLOS ONE Volume: 11
  • DOI: 10.1371/journal.pone.0149462
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Resveratrol exerts a biphasic effect on apolipoprotein M (2016)
  • Author(s): Kurano M, Hara M, Nojiri T, Ikeda H, Tsukamoto K, Yatomi Y.
  • Journal Title: Br. J. Pharmacol. Volume: 173 Pages: 222-233
  • DOI: 10.1111/bph.13360
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] リコンビナントアポ蛋白Mを利用した多臓器不全に対する新規治療法の開発． (2016)
  • Author(s): 蔵野 信，矢冨 裕．
  • Organizer: 第56回 日本臨床化学会年次学術集会．
  • Place of Presentation: 熊本
  • Year and Date: 2016-12-03
• [Presentation] Sphingosine 1-Phosphate Possesses the Carrier-dependent Effects on the Plasminogen Activator Inhibitor 1 Expression in Adipocytes. (2016)
  • Author(s): Takahashi, C., Kurano, M., Nishikawa, M., Kano, K., Dohi, T., Miyauchi, K., Daida, H., Shimizu, T., Aoki, J., and Yatomi, Y.
  • Organizer: AHA Scientific Sessions 2016.
  • Place of Presentation: New Orleans, Louisiana, USA.
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Carrier-dependent Effects of Sphingosine 1-phosphate on Plasminogen Activator Inhibitor-1 Expression in Adipocytes. (2016)
  • Author(s): Takahashi, C., Kurano, M., Nishikawa, M., and Yatomi, Y.
  • Organizer: The 9th Congress of the Asia Pacific Society on Thrombosis and Hemostasis
  • Place of Presentation: Taipei, Chinese Taipei.
  • Year and Date: 2016-10-06
  • Int'l Joint Research
• [Presentation] アポ蛋白Ｍを用いた播種性血管内凝固症候群，多臓器不全の新規治療法の開発 (2016)
  • Author(s): 蔵野 信，常山 幸一，常名 政弘，矢冨 裕．
  • Organizer: 第38回 日本血栓止血学会学術集会
  • Place of Presentation: 奈良
  • Year and Date: 2016-06-16
• [Presentation] アポ蛋白Mを用いた播種性血管内凝固症候群、多臓器不全の新規治療法の開発 (2016)
  • Author(s): 蔵野 信、常山 幸一、常名 政弘、矢冨 裕
  • Organizer: 第38回日本血栓止血学会学術集会
  • Place of Presentation: 奈良春日野国際フォーラム（奈良・奈良市）
  • Year and Date: 2016-06-16
• [Presentation] アポ蛋白Mを通じたスフィンゴシン1-リン酸学の構築． (2015)
  • Author(s): 蔵野 信
  • Organizer: 第55回 日本臨床化学会学術集会
  • Place of Presentation: 大阪大学コンベンションセンター（大阪・吹田市）
  • Year and Date: 2015-10-31
  • Invited
• [Book] 実験医学 増刊号 (2015)
  • Author(s): 蔵野 信，可野 邦行，矢冨 裕，青木 順賢
  • Total Pages: 221
  • Publisher: 羊土社
• [Remarks] 東京大学医学部附属病院 検査部
  • URL: http://lab-tky.umin.jp/index.html