Analysis of cell-cell interaction among hepatic non-parenchymal

• Project/Area Number: 22590719
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: TANAKA Minoru 東京大学, 分子細胞生物学研究所, 准教授 (80321909)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 細胞間相互作用 / 肝線維化 / サイトカイン / 細胞間相互 / 発生・分化 / 肝臓学

Research Abstract

Hepatic sinusoid is composed of stellate cells (HSCs) and sinusoidalendothelial cells. In this study, we focused on cell-cell interaction between HSCs and theother non-parenchymal cells (NPCs) at liver fibrosis. We found that Oncostatin M (OSM)directly induced TIMP-1 expression in HSCs and contributed to liver fibrosis bysuppressing the digestion of collagen fiber. Furthermore, OSM seemed to induce theactivation of HSCs indirectly via NPCs. Finally, overexpression of OSM in liver resulted infibrosis without apparent hepatic injury.

Research Products

• [Journal Article] Nephronectin is upregulated in acute and chronic hepatitis and aggravates liver injury by recruiting CD4 positive cells (2013)
  • Author(s): Inagaki F., Tanaka M., Inagaki N., Yagai T., Sato Y., Sekiguchi K., Oyaizu N., Kokudo N., and Miyajima A
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 430 Issue: 2 Pages: 751-756
  • DOI: 10.1016/j.bbrc.2012.11.076
  • Peer Reviewed
• [Journal Article] Identification and isolation of adult liver stem/progenitor cells. (2012)
  • Author(s): Tanaka M, Miyajima A.
  • Journal Title: Methods Mol Biol. Volume: 826 Pages: 25-32
  • DOI: 10.1007/978-1-61779-468-1_3
  • ISBN: 9781617794674, 9781617794681
• [Journal Article] Identification and isolation of adult liver stem/progenitor cells (2012)
  • Author(s): Tanaka M, Miyajima A
  • Journal Title: Methods Mol Biol. Volume: 826 Pages: 25-32
• [Journal Article] TROP2 expressed in the trunk of theureteric duct regulates branching mrphogenesis during kidney development (2011)
  • Author(s): Tsukahara Y, Tanaka M, Miyajima A
  • Journal Title: PLoS One Volume: 6(12) Issue: 12 Pages: 28607-28607
  • DOI: 10.1371/journal.pone.0028607
  • Peer Reviewed
• [Journal Article] Liver stem/progenitor cells : their characteristics and regulatory mechanisms. (2011)
  • Author(s): Tanaka M, Itoh T, Tanimizu N, Miyajima A
  • Journal Title: J Biochem Volume: 149(3) Issue: 3 Pages: 231-239
  • DOI: 10.1093/jb/mvr001
  • NAID: 10030583627
  • Peer Reviewed
• [Journal Article] Kubin T et al(13 人中8番目) (2011)
  • Journal Title: Cel l Stem Cel l Volume: 9(5) Pages: 420-432
  • Peer Reviewed
• [Journal Article] TROP2 expressed in the trunk of the ureteric duct regulates branching mrphogenesis during kidney development (2011)
  • Author(s): Tsukahara Y, Tanaka M, Miyajima A
  • Journal Title: PLoS One Volume: 6(12)
  • Peer Reviewed
• [Journal Article] Liver stem/progenitor cells : their characteristics and regulatory mechanisms (2011)
  • Author(s): Tanaka M, Itoh T, Tanimizu N, Miyajima A
  • Journal Title: J Biochem. Volume: 149 Pages: 231-239
  • NAID: 10030583627
  • Peer Reviewed
• [Journal Article] Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling (2011)
  • Author(s): Kubin T, Poling J, Kostin S, Gajawada P, Hein S, Rees W, Wietelmann A, Tanaka M, Lorchner H, Schimanski S, Szibor M, Warnecke H, Braun T
  • Journal Title: Cell Stem Cell Volume: 9(5) Pages: 420-432
  • Peer Reviewed
• [Journal Article] 細胞間相互作用による肝幹細胞の発生-分化の制御機構 (2011)
  • Author(s): 伊藤暢、田中稔
  • Journal Title: 「実験医学」特集/分子・細胞から解明する肝臓のバイオロジー Volume: 29巻13号 Pages: 2078-2083
• [Journal Article] Characterization and functional analyses of hepatic mesothelial cells in mouse liver development. (2010)
  • Author(s): Onitsuka I, Tanaka M, Miyajima A
  • Journal Title: Gastroenterology Volume: 138 Pages: 1525-1535
  • NAID: 40017376757
  • Peer Reviewed
• [Journal Article] A novel regulatory mechanism for Fgf18 signaling involving cysteine-rich FGF receptor (Cfr) and Delta-like protein (Dlk). (2010)
  • Author(s): Miyaoka Y, Tanaka M, Imamura T, Takada S, Miyajima A.
  • Journal Title: Development Volume: 137 Pages: 159-167
  • Peer Reviewed
• [Journal Article] p130Cas plays essential roles in liver development by regulating sinusoidal endothelial cell fenestration. (2010)
  • Author(s): Tazaki T, Sasaki T, Uto K, Yamasaki N, Tashiro S, Sakai R, Tanaka M, Oda H, Honda Z, Honda H.
  • Journal Title: Hepatology Volume: 52 Pages: 1089-99
  • Peer Reviewed
• [Presentation] オンコスタチン M はマクロファージの M1/M2 バランスに作用しインスリン抵抗性を改善する 発表者 (2012)
  • Author(s): 田中稔
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
  • Year and Date: 2012-12-16
• [Presentation] オンコスタチンMはマクロファージのM1/M2バランスに作用しインスリン抵抗性を改善する 発表者 (2012)
  • Author(s): 田中稔
  • Organizer: 第19回肝細胞研究会
  • Place of Presentation: 札幌医科大学
  • Year and Date: 2012-06-29
• [Presentation] Characterization of hematopoieticniches in mouse fetal live (2012)
  • Author(s): 田中稔
  • Organizer: 10thISSCR annual meeting
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-15
• [Presentation] Identification of fetal liver cellscontributing to hematopoiesis duringmouse embryogenesis (2010)
  • Author(s): 田中稔
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] Identification of fetal liver cells contributing to hematopoiesis during mouse embryogenesis (2010)
  • Author(s): Tanaka M.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] Identification of fetal liver cellscontributing to hematopoiesis duringmouse embryogenesis (2010)
  • Author(s): 田中稔
  • Organizer: FASEB SummerResearch Conference
  • Place of Presentation: アメリカ・Snowmass
  • Year and Date: 2010-08-18
• [Presentation] Identification of fetal liver cells contributing to hematopoiesis during mouse embryogenesis (2010)
  • Author(s): Tanaka M.
  • Organizer: FASEB Summer Conference
  • Place of Presentation: コロラド州、Snowmass
  • Year and Date: 2010-08-18
• [Presentation] オンコスタチンMはマクロファージのM1/M2バランスに作用しインスリン抵抗性を改善する
  • Author(s): 田中稔、小森 忠祐、森川吉博、仙波恵美子、宮島篤
  • Organizer: 第85回 日本生化学会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
• [Presentation] オンコスタチンMはマクロファージのM1/M2バランスに作用しインスリン抵抗性を改善する
  • Author(s): 田中稔、小森 忠祐、森川吉博、仙波恵美子、宮島篤
  • Organizer: 第19回 肝細胞研究会
  • Place of Presentation: 札幌医科大学
• [Book] Identification and isolation of adult liverstem/progenitor cells (2012)
  • Author(s): Tanaka M, Miyajima A
  • Publisher: Methods Mol Bi o
• [Book] マーカー分子による肝幹/前駆細胞の性状解析 (2012)
  • Author(s): 田中稔
  • Publisher: 生化学
• [Book] 細胞間相互作用による肝幹細胞の発生・分化の制御機構 (2011)
  • Author(s): 伊藤暢 田中稔
  • Publisher: 実験医学(29巻13号8月号)羊土社
• [Book] Liver stem cells. (2011)
  • Author(s): Itoh T, Tanaka M,Miyajima A
  • Publisher: Regenerati ve Medi ci ne f rom Protocol to Pati ent
• [Patent(Industrial Property Rights)] 非アルコール性脂肪肝炎モデル非ヒト哺乳動物及びその作製方法 (2012)
  • Inventor(s): 宮島篤、田中稔
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: 2011-208354
  • Filing Date: 2012-06-28
• [Patent(Industrial Property Rights)] オンコスタチンM受容体シグナリング (2011)
  • Inventor(s): 森川吉博、宮島篤、田中稔、小森忠
  • Industrial Property Rights Holder: 森川吉博、宮島篤、田中稔、小森忠
  • Filing Date: 2011-09-26