Role of sphingolipids on hepatocyte apoptosis of chronic liver injury

• Project/Area Number: 19790478
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Gifu University
• Principal Investigator: OSAWA Yosuke Gifu University, 大学院医学系研究科, 助教授 (60447787)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,750,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: 慢性肝障害 / アポトーシス / クッパー細胞 / 肝線維化 / スフィンゴミエリナーゼ / 肝再生 / スフィンゴ脂質

Research Abstract

胆管結紮により誘導される慢性肝障害では、クッパー細胞の活性化により障害肝に残存する肝細胞がAKT 活性化を介した抗アポトーシス状態を獲得する。クッパー細胞は、肝障害に対し抑制的に作用する役割を有する。

Research Products

• [Journal Article] Sphingosine kinase isoforms regulate oxaliplatin sensitivity of human colon cancer cells through ceramide accumulation and AKT activtion (2009)
  • Author(s): Nemoto, S., Nakamura, M., Osawa, Y., Kono, S., Itoh, Y., Okano, Y., Murate, T., Hara, A., Ueda, H., Nozawa, Y. , Banno, Y.
  • Journal Title: J Biol Chem (in print)
  • Peer Reviewed
• [Journal Article] Antiapoptotic effect of c-Jun N-terminal Kinase-1 through Mcl-1 stabilization in TNF-induced hepatocyte apoptosis (2009)
  • Author(s): Kodama, Y., Taura, K., Miura, K., Schnabl, B., Osawa, Y. and Brenner, D. A.
  • Journal Title: Gastroenterology 136 Pages: 1423-1434
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2: its paradoxical roles in liver inflammation and fibrosis (2008)
  • Author(s): Osawa, Y. and Nagaki, M.
  • Journal Title: Hepatol Res 38 Pages: 772-774
  • NAID: 10021945849
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 : its paradoxical roles in liver inflammation and fibrosis (2008)
  • Author(s): Osawa Y, Nagaki M
  • Journal Title: Hepatology Research 38 Pages: 123-125
  • NAID: 10021945849
  • Peer Reviewed
• [Journal Article] TLR4 enhances TGF-beta signaling and hepatic fibrosis (2007)
  • Author(s): Seki, E., De Minicis, S., Osterreicher, C. H., Kluwe, J., Osawa, Y., Brenner, D. A., Schwabe, R. F.
  • Journal Title: Nat Med 13 Pages: 1324-1332
  • Peer Reviewed
• [Journal Article] Epimorphin, a morphogenic protein, induces proteases in rodent hepatocytes through NF-kappaB (2007)
  • Author(s): Miura, K., Yoshino, R., Hirai, Y., Goto, T., Ohshima, S., Mikami, K., Yoneyama, K., Watanabe, D., Sato, M., Senoo, H., Kodama, Y., Osawa, Y., Brenner, D. A., Watanabe, S.
  • Journal Title: J Hepatol 47 Pages: 834-843
  • Peer Reviewed
• [Journal Article] Alpha-1 antitrypsin Z protein (PiZ) increases hepatic fibrosis in a murine model of cholestasis (2007)
  • Author(s): Mencin, A., Seki, E., Osawa, Y., Kodama, Y., De Minicis, S., Knowles, M. and Brenner, D. A.
  • Journal Title: Hepatology 46 Pages: 1443-1452
  • Peer Reviewed
• [Journal Article] The Forkhead Transcription Factor FoxO1 Regulates Proliferation and Transdifferentiation of Hepatic Stellate Cells (2007)
  • Author(s): Adachi, M., Osawa, Y., Uchinami, H., Kitamura, T., Accili, D. and Brenner, D. A.
  • Journal Title: Gastroenterology 132 Pages: 1434-1446
  • Peer Reviewed
• [Journal Article] The Forkhead Transcription Factor FoxO1 Regulates Proliferation and Transdifferentiation of Hepatic Stellate Cells (2007)
  • Author(s): Adachi M, Osawa Y
  • Journal Title: Gastroenterology 132 Pages: 1434-46
  • Peer Reviewed
• [Journal Article] Alpha-1 antitrypsin Z protein (PiZ)increases hepatic fibrosis in a mu rine model of cholestasis (2007)
  • Author(s): Mencin A, Osawa Y
  • Journal Title: Hepatology 46 Pages: 1443-1452
  • Peer Reviewed
• [Presentation] Anti-apoptotic effects against TNF-alpha treatment in bile duct ligated mouse liver (2008)
  • Author(s): Osawa Y
  • Organizer: Digestive Disease Week (DDW) 2008
  • Place of Presentation: サンディエゴ
  • Year and Date: 2008-05-22
• [Presentation] Anti-apoptotic effects against TNF-alpha treatment in bile duct ligated mouse liver (2008)
  • Author(s): Osawa Y
  • Organizer: Digestive Disease Week (DDW) 2008
  • Place of Presentation: 米国サンディエゴ
  • Year and Date: 2008-05-21
• [Presentation] 肝星細胞におけるコラーゲン産生にかかわるfocal およびsystemic factor の検討 (2007)
  • Author(s): 大澤 陽介
  • Organizer: 第11 回日本肝臓学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-18
• [Presentation] 肝星細胞におけるコラーゲン産生にかかわるfocalおよびsystemic factorの検計 (2007)
  • Author(s): 大澤 陽介
  • Organizer: 第11回日本肝臓学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-18
• [Presentation] 胆管結紮により誘導された慢性肝障害マウスモデルにおける抗アポトーシス獲得機序 (2007)
  • Author(s): 大澤 陽介
  • Organizer: 第18 回The Meeting of Liver and Immunology
  • Place of Presentation: 京都
  • Year and Date: 2007-09-01
• [Presentation] 胆管結紮により誘導された慢性肝障害マウスモデルにおける抗アポトーシス獲得機序 (2007)
  • Author(s): 大澤 陽介
  • Organizer: 第18回The Meeting of Liver andImmunology
  • Place of Presentation: 京都
  • Year and Date: 2007-09-01
• [Presentation] Systemic Mediators Induce Fibrogenic Effects in Normal Liver after Partial Bile Duct Ligation (2007)
  • Author(s): Osawa Y
  • Organizer: Digestive Disease Week (DDW) 2007
  • Place of Presentation: ワシントンDC
  • Year and Date: 2007-05-22
• [Presentation] Systemic Mediators Induce Fibrogenic Effects in Normal Liver after Partial Bile Duct Ligation (2007)
  • Author(s): Osawa Y
  • Organizer: Digestive Disease Week(DDW)2007
  • Place of Presentation: ワシントンDC
  • Year and Date: 2007-05-22