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1998 Fiscal Year Final Research Report Summary

The expression and regulation of the liver enriched transcription factors involving in liver differentiation

Research Project

Project/Area Number 09670120
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionAkita University

Principal Investigator

SUGIYAMA Toshihiro  Akita University School of Medicine, Professor, 医学部, 教授 (00127242)

Co-Investigator(Kenkyū-buntansha) MIURA Naoyuki  Akita University School of Medicine Associate Professor, 医学部, 助教授 (40165965)
Project Period (FY) 1997 – 1998
KeywordsHNF-4 / HNF-1 / liver enriched transcription factors / oval cells / liver differentiation / liver stem cells / EGF / retinoic acid
Research Abstract

Oval cells function as compensatory cells in severe liver injury and are thought to be equivalent to liver stem/progenitor cells. We isolated oval cells from the liver of Long-Evans Cinnamon (LEC) rats by lsopyknic centrifugation in a Percoll gradient. The cells were gamma-glutamyl transpeptidase (gammaGTP) positive alpha-fetoprotein positive, cytokeratin 18 and 19 positive, but albumin negative in the cells. When oval cells were transplanted to the liver, they were transformed into hepatocytes.
The expression of the liver enriched transcription factors HNF-1 , -3, -4, and C/EBP is concordant with appearance of the differentiated phenotype in the embryos. Albumin gene is activated at the onset of hepatocyte differentiation during embyogenesis. Among liver-enriched transcription factors, only HNF-3beta mRNA was expressed, but HNF-3alpha, HNF-4, HNF-lalpha and C/EBPalpha mRNAs were undetectable.
In vitro experiments, oval cells were cultured in the presence of EGF(10mg/ ml) in three-dimensional collagen gels for 9 days. they formed bile duct-like branchingtubles, On the other hand, oval cells cultured on collagen coated dishes in the presence of retinoic acid expressed HNF-4 gene and gamma GTP protein significantly.
These results indicated that the oval cells isolated from LEC rats can differentiate into hepatocytes in vivo and can differentiate into bile epithelial cells in vitro.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Terada, K.: "Biliary excretion of copper in LEC rat after introduction of copper transporting P-type ATPase, ATP7B." FEBS Lett.in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terada, K.: "Restoration of holoceruloplasmin svnthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA." J.Biol.Chem.273. 1815-1820 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terada K.: "ATP7B(WND)protein." Int.J.Biochem.Cell Biol.30. 1063-1067 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miura N.: "Mouse forkhead(winged helix)gene LUN encodes a transactivator that acts in the lung." Genomics. 50. 346-356 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Awata, R.,: "Morphological comparison and functional reconstitution of rat hepatic parenchymal cells on various matrices" J.Gastroenterol Hepatol.13. S55-61 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawarada, Y.: "Antibody against single-stranded DNA useful for detecting apoptotic cells recognizes hexadeoxynucleotides with various base sequences." J.Biochem.123. 492-498 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terada, K.: "Biliary excretion of copper in LEC rat after introduction of copper transporting P-type ATPase, ATP7B." FEBS Lett.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terada, K.: "Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.3" J.Biol.Chem.273. 1815-1820 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terada K.: "ATP7B (WND) protein." Int.J.Biochem.Cell Biol.30. 1063-1067 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miura N.: "Mouse forkhead (winged helix) gene LUN encodes a transactivator that acts in the lung." Genomics. 50. 346-356 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Awata, R.: "Morphological comparison and functional reconstitution of rat hepatic parenchymal cells on various matrices." J.Gastroenterol.Hepatol.13. S55-61 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawarada, Y.: "Antibody against single-stranded DNA useful for detecting apoptotic cells recognizes hexadeoxynucleotides with various base sequences." J.Biochem.123. 492-498 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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