Liver Biology and Pathobiology

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Hepatoma-derived growth factor is highly expressed in developing liver and promotes fetal hepatocyte proliferation

  1. Hirayuki Enomoto1,
  2. Kenya Yoshida1,
  3. Yoshihiko Kishima1,
  4. Taisei Kinoshita2,†,
  5. Mitsunari Yamamoto1,
  6. Allen D. Everett3,
  7. Atsushi Miyajima2,
  8. Hideji Nakamura1,*

Article first published online: 7 MAR 2007

DOI: 10.1002/hep.1840360629

Issue

Hepatology

Hepatology

Volume 36, Issue 6, pages 1519–1527, December 2002

Additional Information

How to Cite

Enomoto, H., Yoshida, K., Kishima, Y., Kinoshita, T., Yamamoto, M., Everett, A. D., Miyajima, A. and Nakamura, H. (2002), Hepatoma-derived growth factor is highly expressed in developing liver and promotes fetal hepatocyte proliferation. Hepatology, 36: 1519–1527. doi: 10.1002/hep.1840360629

Author Information

  1. 1

    Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

  2. 2

    Laboratory of Cellular Biosynthesis, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan

  3. 3

    Department of Pediatrics, University of Virginia Health Science Center, Charlottesville, VA

  1. †

    RIGEL Inc., 240 East Grand Avenue, South San Francisco, CA 94080

*Department of Molecular Medicine, Osaka University Graduate School of Medicine, 2–2 Yamada-oka Suita, Osaka 565–0871, Japan. fax: (81) 6–6879–3839

Publication History

  1. Issue published online: 7 MAR 2007
  2. Article first published online: 7 MAR 2007
  3. Manuscript Accepted: 7 SEP 2002
  4. Manuscript Received: 19 FEB 2002

Funded by

  • Scientific Research of the Ministry of Education, Culture, Sports, Science, and Technology of Japan

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Abstract

Hepatoma-derived growth factor (HDGF) is a heparin-binding protein, which has been purified from the conditioned media of HuH-7 hepatoma cells. Recent studies have suggested the involvement of HDGF in development of the kidney and cardiovascular systems. In the present study, we investigated the possibility that HDGF was also involved in liver development. Northern blot and immunostaining revealed unique expression patterns of HDGF in liver development. HDGF expression was strongly detected in the fetal liver of the midgestation stage and was markedly decreased near birth. Its expression was mainly detected in stromal cells, including immature hepatocytes. Expression in hepatocytes decreased with differentiation. Administration of recombinant HDGF enhanced the growth of primary cultured fetal hepatocytes significantly, although the effect was small. The effect of exogenous HDGF on the proliferation of neonatal hepatocytes was also small and significant only at one point, despite the lower expression of endogenous HDGF, suggesting that the differences exist between fetal and neonatal hepatocytes. However, adenoviral introduction of HDGF antisense cDNA into the fetal hepatocytes significantly suppressed their proliferation, and the inhibitory effect of HDGF antisense virus was reversed by exogenous HDGF. In conclusion, HDGF helps regulate the hepatocyte proliferation in liver development. (HEPATOLOGY2002;36:1519–1527).

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