Analysis of the function of Oncostatain M in chronic hepatitis andliver fibrosis

• Project/Area Number: 19590383
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: The University of Tokyo
• Principal Investigator: TANAKA Minoru The University of Tokyo, 分子細胞生物学研究所, 特任講師 (80321909)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 疾患モデル動物 / サイトカイン / 細胞組織 / 免疫学 / 肝臓 / 脂肪肝 / 細胞・組織

Research Abstract

肝障害時におけるオンコスタチンM(OSM)の作用機序の解明を目指した。高脂肪食投与による肥満モデルでは、OSM 受容体KO マウスは野生型マウスに比べて有意に体重の増加を示し、肝臓内の脂質量が増加するなど、早期の脂肪肝を引き起こした。OSM はPPARg の発現を抑制することで脂肪肝を抑制していることが示唆された。また、肝炎惹起因子を投与したKO マウスは野生型マウスより感受性が高く、急性肝炎で死亡したことから、OSM には免疫抑制作用があることが示唆された。

Research Products

• [Journal Article] equallycontribution : corresponding author. Potentialhepatic stem cells reside in EpCAM+ cells ofnormal and injured mouse livers (2009)
  • Author(s): Okabe M, Tsukahara Y, Tanaka M, Suzuki K, Saito S, Kamiya Y, Tsujimura T,Nakamura K and Miyajima A.
  • Journal Title: Development 136(11) Pages: 1951-60
  • Peer Reviewed
• [Journal Article] Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse livers (2009)
  • Author(s): Okabe M*, Tsukahara Y*, Tanaka M*T. Suzuki K, Saito S, Kamiya Y, Tsujimura T, Nakamura K, and Miyajima A *, equally contribution, T :corresponding author
  • Journal Title: Development (掲載確定 In press)
  • Peer Reviewed
• [Journal Article] YB-1 downregulates expression of carbamoyl phosphate synthetase-I by suppressine C/EBPaloha function in mice. (2009)
  • Author(s): Chen YR, Sekine K, Nakamura K, Yanai H. Tanaka M, Miyajima A.
  • Journal Title: Gastroenterology (掲載確定 In press)
  • Peer Reviewed
• [Journal Article] Inducible expression of Wnt genes during adult hepatic stem/progenitor cell response. (2009)
  • Author(s): Itoh T, Kamiya Y, Okabe M, Tanaka M, Miyajima A.
  • Journal Title: FEBS Letter 583(4) Pages: 777-781
  • Peer Reviewed
• [Journal Article] equally contribution.p75 neurotrophin receptor is a marker forprecursors of stellate cells and portal fibroblastsin mouse fetal liver (2008)
  • Author(s): Suzuki K, Tanaka M, Watanabe N, Saito S,Nonaka H, Miyajima A
  • Journal Title: Gastroenterology 135(1) Pages: 270-281
  • Peer Reviewed
• [Journal Article] OncostatinM receptor-beta signaling limits monocytic cellrecruitment in acute inflammation (2008)
  • Author(s): Hams E et.al.
  • Journal Title: J.Immunology 181(3) Pages: 2174-80
  • Peer Reviewed
• [Journal Article] p75 neurotrophin receptor is a marker for precursors of stellate cells and portal fibroblasts in mouse fetal liver (2008)
  • Author(s): Suzuki K*, Tanaka M*, Watanabe N , Saito S, Nonaka H, Miyajima A *, equally contribution
  • Journal Title: Gastroenterology 135(1) Pages: 270-281
  • Peer Reviewed
• [Journal Article] Junctional adhesion molecule-A, JAM-A, is a novel cell-surface marker for long-term repopulating hematopoietic stem cells. (2008)
  • Author(s): Sugano Y, Takeuchi M, Hirata A, Matsushita H, Kitamura T, Tanaka M, Miyajima A.
  • Journal Title: BLOOD 111 Pages: 1163-1172
  • Peer Reviewed
• [Journal Article] Oncostatin M receptor-beta signaling limits monocytic cell recruitment in acute inflammation (2008)
  • Author(s): Hams E, Colmont CS, Dioszeghy V, Hammond VJ, Fielding CA, Williams AS, Tanaka M, Miyajima A, Taylor PR, Torley N, Jones SA.
  • Journal Title: Journal of Immunology 181 Pages: 2174-2180
  • Peer Reviewed
• [Journal Article] OncosatainM gene therapy attenuates liver damage inducedby dimethynitorsoamine in rats (2007)
  • Author(s): Hamada T.et.al.
  • Journal Title: Am. J. Pathol. 171 Pages: 872-881
  • Peer Reviewed
• [Journal Article] Development of murine hepaticsinusoidal endothelial cells characterized by theexpression of hyaluronan receptors (2007)
  • Author(s): Nonaka H., Tanaka M., Suzuki K. and Miyajima A
  • Journal Title: Dev. Dyn 236 Pages: 2258-2267
  • Peer Reviewed
• [Journal Article] Tim2 is expressed in mouse fetal hepatocytes and regulates their differentiation (2007)
  • Author(s): Watanabe N., Tanaka M., Suzuki K., Kumanogoh A., Kikutani H., Miyajima
  • Journal Title: Hepatology 45 Pages: 1240-1249
  • Peer Reviewed
• [Journal Article] Development of murine hepatic sinusoidal endothelial cells characterized by the expression of hyal (2007)
  • Author(s): Nonaka H, Tanaka M, Suzuki K, Miyajima A
  • Journal Title: Dev. Dyn. 236 Pages: 2258-2267
  • Peer Reviewed
• [Journal Article] Oncostatin M gene therapy attenuates liver damage induced by dimethylnitrosamine in rats (2007)
  • Author(s): Hamada T, Sato A, Hirano T, Yamamoto T, Son G, Onodera M, Torii I, Nishigami T, Tanaka M, Miyajima A, Nishiguchi S, Fujimoto J, Tsujimura T.
  • Journal Title: Am J Pathol. 171(3) Pages: 872-81
  • Peer Reviewed
• [Presentation] 肝幹細胞の分離と性状解析 (2008)
  • Author(s): 田中稔
  • Organizer: 肝細胞研究会
  • Place of Presentation: 静岡
  • Year and Date: 2008-06-28
• [Presentation] 肝幹細胞の分離と性状解析 (2008)
  • Author(s): 田中稔
  • Organizer: 肝細胞研究会
  • Place of Presentation: 岡県男女協同参画センターあざれあ
  • Year and Date: 2008-06-28
• [Presentation] 抗p75NTR 抗体を用いた胎生肝臓における間葉系前駆細胞の分離 (2007)
  • Author(s): 田中稔
  • Organizer: 同定BMB2007(日本分子生物学会・日本生化学会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2007-12-12
• [Presentation] 抗p75NTR抗体を用いた胎生肝臓における間葉系前駆細胞の分離・同定 (2007)
  • Author(s): 田中稔, 鈴木香, 斎藤滋, 宮島篤
  • Organizer: 日本分子生物学会・日本生化学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-12