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Protecting mechanism of hepatocyte growth factor against liver fibrosis and cirrhosis.

Research Project

Project/Area Number 09671345
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKansai Medical University

Principal Investigator

KWON A-hon  Kansai Medical University, First Department of Surgery, Associate Professor, 医学部, 助教授 (70225605)

Co-Investigator(Kenkyū-buntansha) MATSUI Yoichi  Kansai Medical University, First Department of Surgery, Assistant Professor, 医学部, 助手 (60278637)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2000: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Keywordshepatocyte growth factor / liver cirrhosis / ischemia and reperfusion / heat shock protein / nitric oxide / 肝再生 / 脂質代謝
Research Abstract

1) Stimulation of liver regeneration and function after partial hepatectomy in cirrhotic rats by continuous infusion of recombinant human hepatocyte growth factor.
We performed 45% hepatectomy in rats with cirrhosis induced by thioacetamide, and administered recombinant human hepatocyte growth factor (HGF). HGF stimulated an increase in the wet weight of the remnant liver compared with untreated control rats. The proliferating cell nuclear antigen labeling index showed that this increase resulted from the stimulation of DNA synthesis. Serum levels of liver enzymes increased after hepatectomy, but returned to the prehepatectomy level more rapidly in rhHGF-treated rats than in controls. rhHGF increased hepatic protein synthesis above prehepatectomy levels and also markedly increased the serum levels of hepatic lipid metabolites. (Journal of Hepatology, 27, 1997)
2) Hepatocyte growth factor stimulates synthesis of lipids and secretion of lipoproteins in rat hepatocytes.
Isolated cells were c … More ultured in the presence or absence of rhHGF for 2 days. During the first 12 hours, rhHGF transiently inhibited the release of lipids. [3H]-glycerol experiment with the transcriptional and translational inhibitors revealed that rhHGF stimulated de novo synthesis of lipids by affecting activities of lipid metabolic gene. [35S]-Methionine experiment also revealed de novo synthesis of apolipoprotein B by rhHGF.Genistein, a tyrosine kinase inhibitor, blocked the secretion of VLDL, as well as synthesis of lipids and apolipoprotein B stimulated by rhHGF.(Hepatology 25, 1997)
3) Recombinant human hepatocyte growth factor protects the liver against hepatic ischemia and reperfusion injury in rats.
Rats were subjected to total or segmental hepatic ischemia by occluding the hepatic artery, portal vein, and bile duct with a microvascular clip. Rats were treated with four intravenous injections of recombinant human HGF.None of the eight animals in the control group were alive 12 h after total hepatic WI/Rp. Seven of eight animals in the rhHGF-treated group were alive more than 2 days after the reperfusion. In the model of segmental hepatic ischemia, rhHGF inhibited the increase in cytokine-induced neutrophil chemoattractant in serum. The number of neutrophils infiltrating the liver was significantly lower in the rhHGF-treated group than in the control group. rhHGF prevented increases in the activity of serum alanine transaminase and in hepatic necrosis. Experiments with proliferating cell nuclear antigen staining demonstrated that hepatocyte proliferation markedly increased in rhHGF-treated rats as compared with controls. (Journal of Surgical Research, 92, 2000)
4) Hypoxia and heat inhibit inducible nitric oxide synthase gene expression by different mechanisms in rat hepatocytes.
we found that hypoxia and heat markedly inhibited the induction of nitric oxide production stimulated by IL-1beta in rat cultured hepatocytes. Both treatments also abolished the induction of iNOS protein and mRNA.However, hypoxia could not prevent either degradation of an inhibitory protein (IkappaBalpha) of nuclear factor-kappaB (NF-kappaB) or translocation of NF-kappaB to the nucleus, whereas heat inhibited both of the IkappaBalpha degradation and NF-kappaB translocation. Transfection experiments with iNOS promoter construct revealed that hypoxia as well as heat significantly inhibited the transactivation of iNOS gene. Further, a hypoxia-response element located in the promoter was not involved in the inhibition of iNOS induction by hypoxia. (Hepatology, 32. 2000) Less

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

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Inoue T, et al.: "Hypoxia and heat inhibit inducible nitric oxide synthase gene expression by different mechanisms in rat hepatocytes"Hepatology. 32. 1037-1044 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakakura Y, et al.: "Recombinant human hepatocye growth factor protects the liver against hepatic ischemia and reperfusion injury in rats."Journal of Surgical Research. 92. 261-266 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tu W, et al..: "An enhancement of nitric oxide production regulates energy metabolism in rat hepatocytes after a partial hepatectomy."Journal of Hepatology. 30. 944-950 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaibori M, et al.: "Hepatocyte growth factor stimulates synthesis of lipids and secretion of lipoproteins in rat hepatocytes.."Hepatology. 27. 1354-1361 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kwon AH, et al.: "Preoperative determination of the surgical procedure for hepatectomy using technetium-99m-galactosyl human serum albumin (99m Tc-GSA) liver scintigraphy"Hepatology. 25. 426-429 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaibori M, et al.: "Stimulation of liver regeneration and function after partial hepatectomy in cirrhotic rats by continuous infusion of recombinant human hepatocyte growth factor."Journal of Hepatology. 27. 381-390 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inoue T, Kwon AH, Oda M, Kaibori M, Kamiyama Y, Nishizawa M, Ito S, Okumura T.: "Hypoxia and heat inhibit inducible nitric oxide synthase gene expression by different mechanisms in rat hepatocytes."Hepatology. 32. 1037-1044 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakakura Y, Kaibori M, Oda M, Okumura T, Kwon AH, Kamiyama Y.: "Recombinant human hepatocyte growth factor protects the liver against hepatic ischemia and reperfusion injury in rats."Journal of Surgical Research. 92. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tu W, Kitade H, Kaibori M, Nakagawa M, Inoue T, Kwon A-H, Okumura T, Kamiyama Y.: "An enhancement of nitric oxide production regulates energy metabolism in rat hepatocytes after a partial hepatectomy."Journal of Hepatology. 30. 944-950 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaibori M, Kwon AH, Oda M, Kamiyama Y, Kitamura N, Okumura T.: "Hepatocyte growth factor stimulates synthesis of lipids and secretion of lipoproteins in rat hepatocytes."Hepatology. 27. 1354-1361 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kwon AH, Ha-Kawa S, Uetsuji S, Inoue T, Matsui Y, Kamiyama Y.: "Preoperative determination of the surgical procedure for hepatectomy using technetium-99m-galactosyl human serum albumin (99mTc-GSA) liver scintigraphy."Hepatology. 25. 426-429 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaibori M, Kwon AH, Nakagawa M, Tu W, Uetsuji S, Kamiyama Y, Okumura T, Kitamura N.: "Stimulation of liver regeneration and function after partial hepatectomy in cirrhotic rats by continuous infusion of recombinant human hepatocyte growth factor."Journal of Hepatology. 27. 381-390 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Inoue et al.: "Hypoxia and Heat Inhibit Inducible Nitric Oxide Synthase Gene Expression by Different Mechanisms in Rat Hepatocytes"Hepatology. 32. 1037-1044 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] A-H.Kwon et al.: "Perioperative blood transfusion in hepatocellular carcinomas : the influence of immunological profile and recurrence-free survival."Cancer. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Sakakura et al.: "Recombinant human hepatocyte growth factor protects the liver against hepatic ischemia and reperfusion injury in rats."Journal of Surgical Research. 92. 261-266 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Kaibori et al.: "Role of hepatocyte growth factor in hepatic ischemia and reperfusion injury"Transplantation Proceeding. 32. 2285-2286 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Satoi et al.: "Nitric oxide production and hepatic dysfunction in patients with postoperative sepsis."Clin Exp Pharmacol Physiol. 27. 197-201 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Satoi et al.: "Increased extra domain-A containing fibronectin and hepatic dysfunction during septic response : an in vivo and in vitro study."Shock. 13. 492-496 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Yoshida et al.: "A novel conception for liver preservation at a temperature just above freezing point"Journal of Surgical Research. 81. 216-223 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] N.Nakamura et al.: "Ex vivo liver perfusion with arterial blood from a pig with ischemic liver failure"Artificial Organs. 23. 153-160 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Satoi et al.: "Different responses to surgical stress between extra domain a+and plasma fibronectins"Clinical and Experimental Pharmacology and Physiology. 26. 225-229 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] W.Tu et al.: "An enhancement of nitric oxide production regulates energy metabolism in rat hepatocytes after a partial hepatectomy"Journal of Hepatology. 30. 994-950 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] AH.Kwon et al.: "Functional hepatic volume measured by technetium-99m-galactosyl-human serum albumin liver scintigraphy:comparison between hepatocyte volume and liver volume by computed tomography"World Journal of Surgery. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] AH.Kwon et al.: "Preoperative Assessment for Laparoscopic Cholecystectomy:Fesaibility of Using Spiral Computed Tomography" Annals of Surgery. 237. 351-356 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Kamiya et al.: "A Simplified Model of Hypoxic Injury in Primary Cultured Rat Hepatocytes." In Vitro Cellular & Developmental Biology-Animal. 34. 131-137 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Kaibori et al.: "Hepatocyte Growth Factor Stimulates Synthesis of Lipids and Secretion of Lipoproteins in Rat Hepatocytes" Hepatology. 27. 1354-1361 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Satoi et al.: "Prolonged decreases in Plasma Nitrate Levels at early Postoperative Phase after Hepato-Pancreato-Biliary Surgery" Journal of Laboratory and Clinical Medicine. 131. 236-242 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Yoshida et al.: "A Novel Conception for Liver Preservation at a Temperature Just Above Freezing Point" Journal of Surgical Research. 81. 216-223 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] A-H.Kwon, et al.: "Preoperative Determination of the Surgical Procedure for Hepatectomy using Technetium-99m-Galactosyl Human Serum Albumin (99mTc-GSA) Liver Scintigraphy." Hepatology. 25. 426-429 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Kaibori, et al.: "Stimulation of liver regeneration and function after partial hepatectomy in cirrhotic rats by continuous infusion of recombinant human hepatocyte growth factor" Journal of Hepatology. 27. 381-390 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Kaibori, et al.: "Hepatocyte Growth Factor Stimulates Synthesis of Lipids and Secretion of Lipoproteins in Rat Hepatocytes" Hepatology. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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

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