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Molecular Analysis of liver cirrhosis

Research Project

Project/Area Number 06807051
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionNagasaki Univarsity

Principal Investigator

OHTSURU Akira  NAGASAKI UNIVERSITY,SCHOOL OF MEDICINE,Assistant Professor, 医学部, 助手 (00233198)

Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsliver cirrhosis / liver regeneration / PTHrP / PTHrP receptor / AFP / albumin
Research Abstract

To develop the new treatment of liver cirrhosis in Japan, it is essential to investigate on the molecular mechanism of liver cirrhosis. In the present projects, we have concentrated in the transcriptional control mechanism and cytokine expression of tissue regeneration, because liver cirrhosis is thought to be a kind of dis-regurated morphogenesis in the liver regeneration. In the former, we have studied the effect of butyrate in alpha-fetoprotein (AFP) and albumin gene expression using the differentiated liver cancer cell lines. In the later, we have analyzed the pathophysiological role of parathyroid-hormone-related peptide (PTHrP) in morphogenesis and oncogenesis.
The study of upstream regulatory element of AFP has clarified that the CCAAT box is important in the switching mechanism from AFP to albumin gene expression. These data are speculated that the genes involving liver cirrhosis might be controlled by C/EBP (Gastroenterology 107 : 499-504,1994).
In tissue regeneration, such as l … More iver regeneration, PTHrP is a key cytokine regulated the cell motility and apoptosis (Endocrinology 134 : 1936-1942,1994. Arterioscl Throm Vascul Biol in press 1996). Increased PTHrP expression is also demonstrated to be involved the fibrosis in other organ (J Pathol 175 : 227-236, 1995). Furthermore, we have applied the antisense PTHrP oligonucleotide therapy against PTHrP producing pituitary tumor which is newly established in our laboratory (Cancer Res 56 : 77-86,1996).
To further extend the basic research, we have focused on the critical events of liver cirrhosis induced by abnormal expression of cytokines escaping from physiological regeneration or apoptosis, which can eventually induce gene instability and abnomal cell proliferation. The experimental design is in vivo rat animal model which is implanted with PTHrP producing pituitary tumor, previously described. Surprisingly, these rats are developed the liver fibrosis and splenomegaly in 3 months after tumor cell inoculation, and also developed the liver cancer 4 months after tumor implantation.
Further studies are planned on clarification of molecular mechanism of cytokine induced liver cirrhosis using This in vivo experimental systems.
Finally, we acknowledge a support from this grant and a valuable contribution of our post doc fellows and staffs. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Tsutsumi T, et al.: "Reciprocal regulation of α-fetoprotein and albumin gene expression by butyrate in human hepatoma cells." Gastroenterology. 107. 499-504 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ito M, et al.: "Expression of parathyroid homone-related peptide in relation to perturbations of gastric motility in the rat." Endocrinology. 134. 1936-1942 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hamasaki K, et al.: "Changes in the prevalence of HBeAg-negative mutant hepatitis B virus during the course of chronic hepatitis B." Hepatology. 20. 8-14 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakashima M, et al.: "Expression of parathyroid hormone-related peptide in human tumors." J. Pathology. 175. 227-236 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Akino K, et al.: "Antisense inhibition of parathyroid hormone-relate peptide gene expression reducesmaliganant pituitary tumor progression and metastases." Cancer Res. 156. 77-89 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ozeki S,et al.: "Evidence that implicates the parathyroid hormone-related peptide in vascular stenosis." Arterioscler Thromb Vasc Biol. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T,Tsutsumi, et al.: "Reciprocal regulation of alpha-fetoprotein and albumin gene expression by butyrate in human hepatoma cells.19GC01 : Gastroenterology" 107. 499-504 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Hamasaki, et al.: "Changes in the prevalence of HBeAg-negative mutant hepatitis B virus during the course of chronic hepatitis B." Hepatology. 20. 8-14 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Ito, at al.: "Expresson of parathyroid hormone-related peptide in relation to perturbations of gastric motility in the rat." Endocrinology. 134. 1936-1942 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Nakashima, et al.: "Expression of parathyroid hormone-related peptide in human thyroid tumours." J Pathol. 175. 227-236 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Akino, et al.: "Antisense inhibition of parathyroid hormone-related peptide gene expression reduces malignant rat pituitary tumor progression and metastases." Cancer res. 56. 77-86 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Ozeki, et al.: "Evidence implicating parathyroid hormone-related peptide in vascular stenosis : Increased gene expression observed in the intima of injured rat carotid arteries and human restenotic coronary lesions." Arterioscler Thromb Vascul Biol. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsutsumi T,et al.: "Reciprocal regulation of α-fetoprotein and albumin gene expression by butyrate in human hepatoma cells." Gastroenterology. 107. 499-504 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ito M,et al.: "Expression of parathyroid hormone-related peptide in relation to perturbations of gastric motility in the rat." Endocrinology. 134. 1936-1942 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hamasaki K,et al.: "Changes in the prevalence of HBeAg-negative mutant hepatitis B virus during the course of chronic hepatitis B." Hepatology. 20. 8-14 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakashima M,et al.: "Expression of parathyroid hormone-related peptide in human thyroid tumors." J.Pathology. 175. 227-236 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Akino K,et al.: "Antisense inhibition of parathyroid hormone-relate peptide gene expression reduces maliganant pituitary tumor progression and metastases." Cancer Res. 156. 77-89 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ozeki S,et al.: "Evidence that implicates the parathyroid hormone-related peptide in vascular stenosis." Arterioscler Thromb Vasc Biol. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsutsumi T,et al.: "Reciprocal regulation of α-fetoprotein and albumin gene expression by butyrate in human hepatoma cells." Gastroenterology. 107. 499-504 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ito M,et al.: "Expression of parathyroid hormone-related peptide in relation to perturbations of gastric motility in the rat." Endocrinology. 134. 1936-1942 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nakayama T,et al.: "Coronary atherosclerotic smooth muscle cells overexpress human parathyroid hormone-related peptides" Biochem Biophys Res Communm. 200. 1028-1035 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hamasaki K,et al.: "Changes in the prevalence of HBeAg-negative mutant hepatitis B virus during the course of chronic hepatitis B" Hepatology. 20. 8-14 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Usa T,et al.: "Correlation between supression of c-myc and antiproliferative effect of transforming growth factor β1 in the thyroid carcinoma cell growth." Endocrinology. 135. 1378-1384 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nakashima M,et al.: "Expression of parathyroid hormone-related peptide in human thyroid tumors" J.Pathology. (in press). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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