Stimulation of liver regeneration and function by IGF-I

• Project/Area Number: 23590961
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: TOMIYA Tomoaki 東京大学, 医学部附属病院, 特任講師 (90227637)
• Co-Investigator(Kenkyū-buntansha): IKEDA Hitoshi 東京大学, 医学部附属病院, 准教授 (80202422)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 再生医学 / 栄養学 / 肝不全

Research Abstract

Stimulation of proliferation and function by hepatic cells are important for the treatment of liver failure. We studied the stimulatory effect of IGF-I on hepatic cells.
IGF-I activated its receptor on hepatocytes, and stimulated its proliferation as well as protein production and glucose metabolism. These effects were regulated by culture conditions of hepatocytes. In hepatic stellate cells, IGF-I enhanced the proliferation, while collagen production was reduced by IGF-I treatment through the enhancement of collagen degradation.IGF-I stimulates hepatocyte proliferation and function. In addition, it may suppress hepatic fibrosis. IGF-I is a candidate as a drug for the treatment of liver diseases including hepatic failure.

Research Products

• [Journal Article] Treatment for minimal hepatic encephalopathy : Are we ghost busters? (2014)
  • Author(s): Tomiya T
  • Journal Title: Hepatol Res Volume: (in press)
• [Journal Article] High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly-malignant potential (2014)
  • Author(s): Uranbileg B, Enooku K, Soroida Y, Ohkawa R, Kudo Y, Nakagawa H, Tateishi R, Yoshida H, Shinzawa S, Moriya K, Ohtomo N, Nishikawa T, Inoue Y, Tomiya T, Koike K, Yatomi Y, Ikeda H
  • Journal Title: Int J Cancer Volume: 134 Pages: 2189-2198
• [Journal Article] Expression ofα-taxilin in the murine gastrointestinal tract : potential implication in cell proliferation (2014)
  • Author(s): Horii Y, Sakane H, Nogami S, Ohtomo N, Tomiya T, Shirataki, H
  • Journal Title: Histochem Cell Biol Volume: 141 Pages: 165-180
• [Journal Article] Expression of α-taxilin in the murine gastrointestinal tract: potential implication in cell proliferation. (2014)
  • Author(s): Horii Y, Sakane H, Nogami S, Ohtomo N, Tomiya T, Shirataki H.
  • Journal Title: Histochem Cell Biol. Volume: 141 Issue: 2 Pages: 165-80
  • DOI: 10.1007/s00418-013-1147-0
  • Peer Reviewed
• [Journal Article] Treatment for minimal hepatic encephalopathy: Are we ghost busters? (2014)
  • Author(s): Tomiya T
  • Journal Title: Hepatol Res Volume: in press
  • Peer Reviewed
• [Journal Article] Induction of p53-dependent p21 limits proliferative activity of rat hepatocytes in the presence of hepatocyte growth factor (2013)
  • Author(s): Inoue Y, Tomiya T, Nishikawa T, Ohtomo N, Tanoue Y, Ikeda H, Koike K
  • Journal Title: PLoS One Volume: 8
• [Journal Article] Induction of p53-dependent p21 limits proliferative activity of rat hepatocytes in the presence of hepatocyte growth factor. (2013)
  • Author(s): Inoue Y, Tomiya T, Nishikawa T, Ohtomo N, Tanoue Y, Ikeda H, Koike K.
  • Journal Title: PLoS One. Volume: 8 Issue: 11 Pages: e78346-e78346
  • DOI: 10.1371/journal.pone.0078346
  • Peer Reviewed
• [Journal Article] High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential. (2013)
  • Author(s): Uranbileg B, Enooku K, Soroida Y, Ohkawa R, Kudo Y, Nakagawa H, Tateishi R, Yoshida H, Shinzawa S, Moriya K, Ohtomo N, Nishikawa T, Inoue Y, Tomiya T, Kojima S, Matsuura T, Koike K, Yatomi Y, Ikeda H.
  • Journal Title: Int J Cancer. Volume: 134 Issue: 9 Pages: 2189-98
  • DOI: 10.1002/ijc.28547
  • Peer Reviewed
• [Journal Article] Antagonism of sphingosine 1-phosphate receptor 2 causes a selective reduction of portal vein pressure in bile duct-ligated rodents (2012)
  • Author(s): Kageyama Y, Ikeda H, Watanabe N, Nagamine M, Kusumoto Y, Yashiro M, Satoh Y, Shimosawa T, Shinozaki K, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, Tanoue Y, Yokota H, Koyama T, Ishimaru K, Okamoto Y, Takuwa Y, Koike K, Yatomi Y
  • Journal Title: Hepatology Volume: 56 Pages: 1427-38
• [Journal Article] Interaction ofα-taxilin localized on intracellular components with the microtubule cytoskeleton (2012)
  • Author(s): Horii Y, Nogami S, Kawano Y, Kaneko-Kawano T, Ohtomo N, Tomiya T, Shirataki H
  • Journal Title: Cell Struct Funct Volume: 37 Pages: 111-26
• [Journal Article] Interaction of α-taxilin localized on intracellular components with the microtubule cytoskeleton. (2012)
  • Author(s): Horii Y, Nogami S, Kawano Y, Kaneko-Kawano T, Ohtomo N, Tomiya T, Shirataki H.
  • Journal Title: Cell Struct Funct Volume: 37 Pages: 112-126
  • NAID: 130004137583
  • Peer Reviewed
• [Journal Article] Antagonism of sphingosine 1-phosphate receptor 2 causes a selective reduction of portal vein pressure in bile duct-ligated rats (2012)
  • Author(s): Kegeyama Y
  • Journal Title: Hepatology Volume: 56 Issue: 4 Pages: 1427-1438
  • DOI: 10.1002/hep.25780
  • Peer Reviewed
• [Journal Article] Prediction of hepatocellular carcinoma development by plasma ADAMTS13 in chronic hepatitis B and C (2011)
  • Author(s): Ikeda H, Tateishi R, Enooku K, Yoshida H, Nakagawa H, Masuzaki R, Kondo Y, Goto T, Shiina S, Kume Y, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, Tanoue Y, Ono T, Koike K, Yatomi Y
  • Journal Title: Cancer Epidemiol Biomarkers Prev Volume: 20 Pages: 2204-11
• [Journal Article] Autotaxin as a novel serum marker of liver fibrosis (2011)
  • Author(s): Nakagawa H, Ikeda H, Nakamura K, Ohkawa R, Masuzaki R, Tateishi R, Yoshida H, Watanabe N, Tejima K, Kume Y, Iwai T, Suzuki A, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, Tanoue Y, Omata M, Igarashi K, Aoki J, Koike K, Yatomi Y
  • Journal Title: Clin Chim Acta Volume: 412 Pages: 1201-6
• [Journal Article] Autotaxin as a novel serum marker of liver fibrosis. (2011)
  • Author(s): Nakagawa H, Ikeda H, Nakamura K, Watanabe N, Tejima K, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, Tanoue Y, Omata M, Igarashi K, Aoki J, Koike K, Yatomi Y.
  • Journal Title: Clin Chim Acta Volume: 412 Pages: 1201-6
  • Peer Reviewed
• [Journal Article] Prediction of hepatocellular carcinoma development by plasma ADAMTS13 in chronic hepatitis B and C. (2011)
  • Author(s): Ikeda H, Tateishi R, Enooku K, Yoshida H, Nakagawa H, Masuzaki R, Kondo Y, Goto T, Shiina S, Kume Y, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, Tanoue Y, Ono T, Koike K, Yatomi Y.
  • Journal Title: Cancer Epidemiol Biomarkers Prev Volume: 20 Pages: 2204-11
  • Peer Reviewed
• [Presentation] IGF-I reduces collagen production through induction of collagen degradation via mTOR dependent signaling pathway (2013)
  • Author(s): 西川尚子, 富谷智明, 大友夏子, 井上有希子, 池田均, 白瀧博通, 小池和彦
  • Organizer: 第20回肝細胞研究会
  • Place of Presentation: 大阪
• [Presentation] 肝星細胞コラーゲン産生に対するIGF-Iの調節作用およびその機序の検討 (2013)
  • Author(s): 西川尚子, 富谷智明, 大友夏子, 井上有希子, 池田均, 白瀧博通, 小池和彦
  • Organizer: 第17回日本肝臓学会大会
  • Place of Presentation: 東京
• [Presentation] Insulin-like growth factor I reduces collagen production by hepatic stellate cells even when their proliferative activity is stimulated (2012)
  • Author(s): Nishikawa T, Tomiya T, Ohtomo N, Inoue Y, Ikeda H, Shirataki H, Koike K
  • Organizer: 22nd Conference of the Asian Pacific Association for the Study of the Liver
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Reduction of collagen production by Insulin-like growth factor I is independent of modulation of activation state in hepatic stellate cells (2012)
  • Author(s): Nishikawa T, Tomiya T, Ohtomo N, Inoue Y, Ikeda H, Shirataki H, Koike K
  • Organizer: 63rd Annual Meeting of the American Association for the Study of the Liver Diseases
  • Place of Presentation: Boston, Massachusetts
• [Presentation] 肝星細胞の増殖とコラーゲン産生に対するIGF-Iの影響に関する検討 (2012)
  • Author(s): 西川尚子, 富谷智明, 大友夏子, 井上有希子, 池田均, 白瀧博通, 小池和彦
  • Organizer: 第19回肝細胞研究会
  • Place of Presentation: 札幌
• [Presentation] 肝星細胞におけるコラーゲン産生に対するIGF-Iの直接作用 (2012)
  • Author(s): 西川尚子, 富谷智明, 大友夏子, 井上有希子, 池田均, 白瀧博通, 小池和彦
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢
• [Presentation] Reduction of collagen production by insulin-like growth factor I is independent of activation state of hepatic stellate cells (2012)
  • Author(s): Nishikawa T, Tomiya T, Ohtomo N, Inoue T, Ikeda H, Shirataki H, Koike K.
  • Organizer: The 63rd annual meeting of the American association for the study of liver diseases
  • Place of Presentation: Boston, USA
• [Presentation] 肝星細胞の増殖とコラーゲン産生に対するIGF-I の影響に関する検討 (2012)
  • Author(s): 西川尚子、富谷智明、大友夏子、井上有希子、池田均、白瀧博通、小池和彦
  • Organizer: 第19回肝細胞研究会
  • Place of Presentation: 札幌
• [Presentation] Insulin-like growth factor I reduces collagen production by hepatic stellate cells even when their proliferative activity is stimulated. (2012)
  • Author(s): Nishikawa T, Tomiya T, Ohtomo N, Inoue Y, Ikeda H, Shirataki H, Koike K.
  • Organizer: 22nd Conference of the Asian Pacific Association for the Study of the Liver
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Effect of IGF-I and mechanisms of its action on proliferation and protein production by rat hepatocytes (2011)
  • Author(s): Tanoue Y, Tomiya T, Ohtomo N, Inoue Y, Nishikawa T, Ikeda H, Shirataki H, Koike K, Fujiwara K
  • Organizer: 46th Annual Meeting of the European Association for the Study of the Liver
  • Place of Presentation: Berlin, Germany
• [Presentation] Expression of alpha-taxilin correlates with growth activity and malignant potential of hepatocellular carcinoma (2011)
  • Author(s): Ohtomo N, Shirataki H, Tomiya T
  • Organizer: 16th World Congress on Advances in Oncology and 14th international Symposium on Molecular Medicine
  • Place of Presentation: Rhodes Island, Greece
• [Presentation] 肝細胞に対するIGF-Iの作用点 (2011)
  • Author(s): 田上靖, 富谷智明, 大友夏子, 西川尚子, 井上有希子, 池田均, 白瀧博通, 藤原研司, 小池和彦
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] 新たな肝線維化マーカーとしての血清Autotaxin抗原量 (2011)
  • Author(s): 中川勇人, 池田均, 増崎亮太, 建石良介, 吉田晴彦, 渡邉尚子, 富谷智明, 井上有希子, 西川尚子, 大友夏子, 田上靖, 小池和彦
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] 血中ADAMTS13による肝細胞癌発症予測 (2011)
  • Author(s): 池田均, 建石良介, 榎奥健一郎, 吉田晴彦, 中川勇人, 増崎亮太, 近藤祐爾, 五藤忠, 椎名秀一朗, 富谷智明, 井上有希子, 西川尚子, 大友夏子, 田上靖, 小池和彦
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] Effect of IGF-I and mechanisms of its action on proliferation and protein production by rat hepatocytes. (2011)
  • Author(s): Tanoue Y, Tomiya T, Ohtomo N, Inoue Y, Nishikawa T, Ikeda H, Shirataki H, Koike K, Fujiwara K.
  • Organizer: 46th Annual Meeting of the European Association for the Study of the Liver
  • Place of Presentation: Berlin, Germany
• [Presentation] Expression of alpha-taxilin correlates with growth activity and malignant potential of hepatocellular carcinoma. (2011)
  • Author(s): Ohtomo N, Shirataki H, Tomiya T.
  • Organizer: 16th World Congress on Advances in Oncology and 14th international Symposium on Molecular Medicine(招待講演)
  • Place of Presentation: Rhodes Island, Greece
• [Remarks]
  • URL: http://gastro.m.u-tokyo.ac.jp/med/0202B3B.htm
• [Remarks] 東京大学医学系研究科消化器内科
  • URL: http://gastro.m.u-tokyo.ac.jp/med/home.html
• [Remarks] 消化器内科 医学部 東京大学医学系研究科
• [Remarks]
  • URL: http://gastro.m.u-tokyo.ac.jp/med/home.html