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VEGF can be a vulnerable candidate as a therapeutic agents for severe and fulminant hepatitis?

Research Project

Project/Area Number 09670588
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionFukuoka University (2000)
Kurume University (1997-1999)

Principal Investigator

SAKISAKA Shotaro  School of Medicine, Fukuoka University, Professor, 医学部, 教授 (90158923)

Co-Investigator(Kenkyū-buntansha) OOISHI Masahito  Kurume Univ.Sch.Med.Assistant Prof.(1996-1999), 医学部, 助手 (80289412)
KOGA Hironori  Kurume Univ.Sch.Med.Assistant Prof.(1996-1999), 医学部, 助手 (90268855)
HARADA Masaru  Kurume Univ.Sch.Med.Assistant Prof.(1996-1999), 医学部, 助手 (00241175)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
KeywordsVEGF / Liver regeneration / Hepatocyte / in situ hybridization / sinusoidal endothelial cell / 免疫組織化学 / 血管内皮増殖因子 / 激症肝炎 / 劇症肝炎
Research Abstract

Vascular endothelial growth factor (VEGF) has been shown to play a major role in angiogenesis, which is essential for both healing of injured tissue and proliferation of carcinoma cells. In this study, we elucidated the expression and role of VEGF in rat liver regeneration after partial hepatectomy. VEGF expression was mainly detected in periportal hepatocytes and reached a maximum level 48 hr after partial hepatectomy by both immunohistochemistry and in situ hybridization. Similarly, immunohistochemistry for Ki-67 showed that the proliferative activity of sinusoidal endothelial cells was highest in the periportal area and reached a maximum level 96 hr after partial hepatectomy. Moreover, neutralization of VEGF significantly inhibited proliferative activity of hepatocytes (P<.0001), as well as sinusoidal endothelial cells (P<.001). Conversely, injection of VEGF singificantly promoted proliferative activity of hepatocytes (P<.0001), as well as sinusoidal endothelial cells (P<.0005). These results suggest that VEGF promotes proliferation of hepatocytes through reconstruction of liver sinusoids by proliferation of sinusoidal endothelial cells. Furthermore, these data point to a new therapeutic strategy, the use of VEGF and other hepatocyte growth factors in fulminant or severe acute hepatitis.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Masaru Harada: "Role of vacuolar pH of on the receptor-mediated endocytosis of horseradish peroxidase in isolate rat sinusoidal endothelial cells."Cell of the hepatic Sinusoid. 6. 384-386 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masaru Harada: "Bafilomycin A1, a specific inhibitor of V-type H+-ATPases, inhibits the acidification of endocytic structuers and inhibits horseradish peroxidase uptake in isolated rat sinusoidal endothelial cells"Liver. 17・5. 244-250 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 谷口英太郎: "再生肝におけるVEGFの発現の検討"薬理と治療(Jpn Pharmacol Ther). 27・7. S863-S865 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 谷口英太郎: "再生肝における増殖期類洞内皮細胞の肝小葉内分布の検討"薬理と治療(Jpn Pharmacol Ther). 27・7. S1515-S1517 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shotaro Sakisaka: "Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis"Liver. 20・1. 78-87 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masaru Harada: "Role of ATP7B in biliary copper excretion in a human hepatoma cell line and normal rat hepatocytes"Gastroenterology. 118・5. 921-928 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masaru Harada: "High prevalence of anticardiolipin antibodies in hepatitis C virus infection : lack of effects on thrombocytopenia and thrombotic complications"J Gastroenterol. 35・4. 272-277 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takumi Kawaguchi: "Cholestasis with altered structure and function of hepatocyte tight junction and decreased expression of canalicular multispecific organic anion transporter in a rat model of colitis"Hepatology. 31・6. 1285-1295 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masaru Harada: "Copper does not alter the intracellular distribution of ATP7B, a copper-transporting ATPase"Biochem Biophys Res Commun. 275・3. 871-876 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Eitaro Taniguchi: "Expression and Role of Vascular Endothelial Growth Factor in Liver Regeneration After Partial Hepatectomy in Rats"J Histochem Cytochem. 49・1. 121-130 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masaru Harada: "A Mutation of Wilson's disease protein, ATP7B, Is Degraded in the Proteasomes and Forms Protein Aggregates"Gastroenterology. 120・4. 967-974 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takumi Kawaguchi: "Endotoxin Increases Paracellular Permeability of Isolated Rat Hepatocyte Couplets"Hepatology Research. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shotaro Sakisaka: "Alterations in Tight Junction Differ Between primary Biliary Cirrhosis and Primary Sclerosing Cholangitis"Hepatology. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Harada M, Shakado S, Sakisaka S, Tamaki S, Ohishi M, Sasatomi K, Koga H, Mimura Y, Sata M, Tanikawa K: "Role of vacuolar pH of on the receptor-mediated endocytosis of horseradish peroxidase in isolated rat sinusoidal endothelial cells."Cell of the hepatic Sinusoid. 6. 384-386 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Harada M, Shakado S, Sakisaka S, Tamaki S, Ohishi M, Sasatomi K, Koga H, Sata M, Tanikawa K: "Bafilomycin A1, a specific inhibitor of V-type H+-ATPases, inhibits the acidification of endocytic structuers and inhibits horseradish peroxidase uptake in isolated rat sinusoidal endothelial cells"Liver. 17. 244-250 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Taniguchi E, Sakisaka S, Koga H, Kawaguchi T, Sasatomi K, Harada M, Sata M: "Expression of VEGF in liver regeneration"Yakuri to chiryo.(Jpn Pharmacol Ther). 27-7. S863-S865 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Taniguchi E, Sakisaka S, Koga H, Kawaguchi T, Sasatomi K, Harada M, Sata M: "Lovular distribution of VEGF expression in the regenerated liver"Yakuri to chiryo.(Jpn Pharmacol Ther). 27-7. S1515-S1517 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakisaka S, Koga H, Sasatomi K, Ohishi M, Kawaguchi T, Harada M, Taniguchi E, Uchimura Y, Ueno T, Sata M, Tanikawa K: "Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis"Liver. 20-1. 78-87 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Harada M, Sakisaka S, Terada K, Kimura R, Kawaguchi T, Koga H, Taniguchi E, Sasatomi K, Miura N, Suganuma T, Fujita H, Furuta K, Tanikawa K, Sugiyama T, Sata M: "Role of ATP7B in biliary copper excretion in a human hepatoma cell line and normal rat hepatocytes"Gastroenterology. 118-5. 921-928 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Harada M, Fujisawa Y, Sakisaka S, Kawaguchi T, Taniguchi E, Sakamoto M, Sumie S, Sasatomi K, Koga H, Torimura T, Ueno T, Gondo K, Yoshida H, Tanikawa K, Sata M: "High prevalence of anticardiolipin antibodies in hepatitis C virus infection : lack of effects on thrombocytopenia and thrombotic complications"J Gastroenterol. 35-4. 272-277 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawaguchi T,Sakisaka S, Mitsuyama K, Harada M, Koga H, Taniguchi E, Sasatomi K, Kimura R, Ueno T, Sawada N, Mori M, Sata M: "Cholestasis with altered structure and function of hepatocyte tight junction and decreased expression of canalicular multispecific organic anion transporter in a rat model colitis"Hepatology. 31-6. 1285-1295 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Harada M, Sakisaka S, Kawaguchi T, Kimura R, Taniguchi E, Koga H, Hanada S, Baba S, Furuta K, Kumashiro R, Sugiyama T, Sata M: "Copper does not alter the intracellular distribution of ATP7B, a copper-transporting ATPase"Biochem Biophys Res Commun. 275-3. 871-876 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Taniguchi E, Sakisaka S, Matsuo K, Tanikawa K, Sata M: "Expression and Role of Vascular Endothelial Growth Factor in Liver Regeneration After Partial Hepatectomy in Rats"J Histochem Cytochem. 49-1. 121-130 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Harada M, Sakisaka S, Terada K, Kimura R, Kawaguchi T, Koga H, Kim M, Taniguchi E, Hanada S, Suganuma T, Furuta K, Sugiyama T, Sata M: "A Mutation of Wilson's disease protein, ATP7B, Is Degraded in the Proteasomes and Forms Protein Aggregates"Gastroenterology. 120-4. 967-974 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawaguchi T, Sakisaka S, Harada M, Hanada S, Taniguchi E, Koga H, Sasatomi K, Tanikawa K, Sata M: "Endotoxin Increases Paracellular Permeability of Isolated Rat Hepatocyte Couplets"Hepatology Research. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakisaka S, Kawaguchi T, Taniguchi E, Hanada S, Sasatomi K, Koga H, Harada M, Kimura R, Sata M: "Alterations in Tight Junction Differ between Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis"Hepatology. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shotaro Sakisaka: "Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis"Liver. 20・1. 78-87 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masaru Harada: "Role of ATP7B in biliary copper-excretion in a human hepatoma cell line and normal rat hepatocytes"Gastroenterology. 118・5. 921-928 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masaru Harada: "High prevalence of anticardiolipin antibodies in hepatitis C virus infection : lack of effects on thrombocytopenia and thrombotic complications"J Gastroenterol. 35・4. 272-277 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takumi Kawaguchi: "Cholestasis with altered structure and function of hepatocyte tight junction and decreased expression of canalicular multispecific organic anion transporter in a rat model of colitis"Hepatology. 31・6. 1285-1295 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masaru Harada: "Copper does not alter the intracellular distribution of ATP7B, a copper-transporting ATPase"Biochem Biophys Res Commun. 275・3. 871-876 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Eitaro Taniguchi: "Expression and Role of Vascular Endothelial Growth Factor in Liver Regeneration After Partial Hepatectomy in Rats"J Histochem Cytochem. 49・1. 121-130 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masaru Harada: "A Mutation of Wilson's disease protein, ATP7B, Is Degraded in the Proteasomes and Forms Protein Aggregates"Gastroenterology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takumi Kawaguchi: "Endotoxin Increases Paracellular Permeability of Isolated Rat Hepatocyte Couplets"Hepatology Research. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shotaro Sakisaka: "Alterations in Tight Junction Differ between Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis"Hepatology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 谷口 英太郎: "再生肝におけるVEGFの発現の検討"薬理と治療(Jpn Pharmacol Ther). 27・7 Suppl.. S863-S865 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 谷口 英太郎: "再生肝における増殖期類洞内皮細胞の肝小葉内分布の検討"薬理と治療(Jpn Pharmacol Ther). 27・7 Suppl.. S1515-S1517 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 谷口 英太郎: "再生肝におけるVEGFの発現の検討" 薬理と治療. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masaru Harada: "Role of vacuolar pH of on the receptor-mediated endocytosis of horseradish peroxidase in isolated rat sinusoidal endothelial cells." Cell of the hepatic Sinusoid. 9. 384-386 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masaru harada: "Bafilomycin A1,a specific inhibitor of V-type H^+-ATPases,inhibits the acidification of endocytic structuers and inhibits horseradish peroxidase uptake in isolated rat sinusoidal endothelial cells" Liver. 17. 244-250 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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