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Hepatotrophic Activities of HGF in Liver Regeneration after Injury and the Clinical Potentiality for Liver Diseases

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Abstract

One of an intriguing, unique property of mammalian liver is its matchless ability to regenerate following injury and to preserve its own optimal size (reviewed in [1]). When 70% of the rat liver is resected, the original liver mass and their functions are almost restored within 10 days. Although there were few cells (no less than 0.1%) undergoing DNA synthesis in the intact liver, hepatocytes begin to proliferate actively when the liver is subjected to several kinds of injury, such as hepatoectomy, ischemia, and hepatitis. It had long been postulated that quiescent hepatocytes were induced to grow by a humoral factor, but its molecular nature remained unknown. We identified and purified a potent mitogenic factor for adult rat hepatocytes, named hepatocyte growth factor (HGF)[2–4]. Molecular cloning of both human and rat HGF cDNAs was achieved in 1989–1990, showing that HGF was a novel growth factor distinct from other known cytokines [5–7]. From our concurrent studies, HGF is now recognised as long-sought, genuine hepatrophic factor functioning in liver regeneration (reviewed in [8–11]). In this chapter we present our work concerning the mechanisms of liver regeneration by HGF and the effective action of HGF for several hepatic dysfunction in vivo.

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References

  1. Fausto, N. and Webber, E.M. (1994). Liver regeneration, In “The Liver: Biology and Pathobiology, 3rd Edition”, eds. Arias, I.M., Boyer, J.L., Fausto, N., Jakoby, W.B., Schachter, D.A. and Shafrots, D.A., Raven Press, New York, pp. 1059–1084.

    Google Scholar 

  2. Nakamura, T., Nawa, K. and Ichihara, A. (1984). Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats, Biochem. Biophys. Res. Commun., Vol. 122, pp. 1450–1459.

    Article  PubMed  CAS  Google Scholar 

  3. Nakamura, T., Teramoto, H. and Ichihara, A. (1986). Purification and characterization of hepatocyte growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures, Proc. Natl. Acad. Sci. USA, Vol. 83, pp. 6489–6493.

    Article  PubMed  CAS  Google Scholar 

  4. Nakamura, T., Nawa, K., Ichihara, A., Kaise, N. and Nishino, T. (1987). Purification and subunit structure of hepatocyte growth factor from rat platelets, FEBS Lett., Vol. 224, pp. 311–318.

    Article  PubMed  CAS  Google Scholar 

  5. Nakamura, T., Nishizawa, T., Hagiya, M., Seki, T., Shimonishi, M., Sugimura, A., Tashiro, K. and Shimizu, S. (1989). Molecular cloning and expression of human hepatocyte growth factor. Nature, Vol. 342, pp. 440–443.

    Article  PubMed  CAS  Google Scholar 

  6. Tashiro, K., Hagiya, M., Nishizawa, T., Seki, T., Shimonishi, M., Shimizu, S. and Nakamura, T. (1990). Deduced primary structure of rat hepatocyte growth factor and expression of the mRNA in rat tissues, Proc. Natl. Acad. Sci. USA, Vol. 87, pp. 3200–3204.

    Article  PubMed  CAS  Google Scholar 

  7. Seki, T., Ihara, I., Sugimura, A., Shimonishi, M., Nishizawa, T., Asami, O., Hagiya, M., Nakamura. T. and Shimizu, S. (1990). Isolation and expression of cDNA for different forms of hepatocyte growth factor from heman leukocytes, Biochem. Biophys. Res. Commun., Vol. 172, pp 321–327.

    CAS  Google Scholar 

  8. Matsumoto, K. and Nakamura, T. (1993). Roles of HGF as a pleiotropic factor in organ regeneration, In “Hepatocyte Growth Factor-Scatter Factor (HGF-SF) and the C-MET Receptor”, eds. Goldberg, I.D. and Rosen, E.M., Birkhauser Verlag, Basel, Switzerland, pp. 225–249.

    Google Scholar 

  9. Matsumoto, K. and Nakamura, T. (1994). Structure, pleiotropic actions, and organotrophic roles of hepatocyte growth factor, In “Liver Carcino genesis: The Molecular Pathways”, NATO ASI Seires, Springer Verlag, pp. 33–53.

    Google Scholar 

  10. Boros, P. and Miller, C.M. (1995). Hepatocyte growth factor: a multifunctional cytokine, Lancet, Vol. 345, pp. 293–295.

    Article  PubMed  CAS  Google Scholar 

  11. Zarnegar, R. and Michalopoulos, G.K. (1995). The many faces of hepatocyte growth factor: from hepatopoiesis to hematopoiesis, J. Cell. Biol., Vol. 129, pp. 1177–1180.

    Article  PubMed  CAS  Google Scholar 

  12. Mizuno, K. and Nakamura, T. (1993). Molecular characteristics of HGF and gene, and its biochemical aspects, In “Hepatocyte Growth Factor-Scatter Factor (HGF-SF) and the C-MET Receptor”, eds. Goldberg, I.D: and Rosen, E.M., Birkhauser Verlag, Basel, Switzerland, pp. 1–29.

    Google Scholar 

  13. Mizuno, K., Tanoue, Y., Okano, I., Harano, T., Takada, K and Nakamura, T. (1994). Purification and characterization of hepatocyte growth factor (HGF)-converting enzyme: Activation of pro HGF, Biochem. Biophys. Res. Commun., Vol. 198, pp. 1161–1169.

    Article  PubMed  CAS  Google Scholar 

  14. Miyazawa, K., Shimomura, T., Naka, D. and Kitamura, N. (1994). Proteolytic activation of hepatocyte growth factor in response to tissue injury, J. Biol. Chem., Vol. 269, pp. 8966–8970.

    PubMed  CAS  Google Scholar 

  15. Bottaro, D.P., Rubin, J.S., Faletto, D.L., Chan, A.M.-I., Kmiecik, T.E., VandeWoude, G.F. and Aaronson, S.A (1991). Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product, Science, Vol. 251, pp. 802–804.

    Article  PubMed  CAS  Google Scholar 

  16. Comoglio, P.M. (1993). Structure, biosynthesis and biochemical properties of the HGF receptor in normal and malignant cells, In “Hepatocyte Growth Factor-Scatter Factor (HGF-SF) and the C-MET Receptor”, eds. Goldberg, I.D. and Rosen, E.M., Birkhauser Verlag, Basel, pp. 131–166.

    Google Scholar 

  17. Ishiki, Y., Ohnishi, H., Muto, Y., Matsumoto, K. and Nakamura, T. (1992). Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and has potent antihepatitis effects in vivo, Hepatology, Vol. 16, pp. 1227–1235.

    PubMed  CAS  Google Scholar 

  18. Kinoshita, T., Tashiro, K. and Nakamura, T. (1989). Marked increase of HGF mRNA in nonparenchymal liver cells of rats treated with hepatotoxins, Biochem. Biophys. Res. Commun., Vol. 165

    Google Scholar 

  19. Noji, S., Tashiro, K., koyama, E., Nohno, T., Ohyama, K., Taniguchi, S. and Nakamura, T. (1990). Expression of hepatocyte growth factor gene in endothelial and Kupffer cells of damaged rat liver, as revealed by in situ hybridization, Biochem. Biophys. Res. Commun., Vol. 173, pp. 42–47.

    Article  PubMed  CAS  Google Scholar 

  20. Kinoshita, T., Hirao, S., Matsumoto, K. and Nakamura, T. (1991). Possible endocrine control by hepatocyte growth factor of liver regeneration after partial hepatectomy, Biochem. Biophys. Res Commun., Vol. 177, pp. 330–335.

    Article  PubMed  CAS  Google Scholar 

  21. Jenkins, S.A., Grandison, A., Bazter, J.N., Day D.W., Taylor, I. and Shields, R. (1985). A dimethylnitrosamïne-induced model of cirrhosis and portal hypertension in the rat, J. Hepatol., Vol. 1, pp. 489–499.

    Article  PubMed  CAS  Google Scholar 

  22. Matsuda, Y., Matsumoto, K, Ichida, T. and Nakamura, T. (1995). Hepatocyte growth factor suppresses the onset of liver cirrhosis and abrogates lethal hepatic dysfunction in rats, J. Biochem., Vol. 1, pp. 643–649.

    Google Scholar 

  23. Czaja, M.J., Weiner, F.R., Flanders, K.C., Giambrone, M., Wind, R., Biempica, L., Zem, M.A. (1989). In vitro and in vivo association of transforming growth factor-ßl with hepatic fibrosis, J. Cell Biol., Vol. 108, pp. 2477–2482.

    Article  PubMed  CAS  Google Scholar 

  24. Nakatsukasa, H., Nagy, P., Everts, R.P., Hsia, C.-C., Marsden, E. and Thorgeirsson, S.S. (1990). Cellular distribution of transforming growth factor-ß1 and procollagen types I, III, and transcripts in carbon tetrachloride-induced rat liver fibrosis, J. Clin. Invest., Vol. 85, pp. 1833–1843.

    Article  PubMed  CAS  Google Scholar 

  25. Nakamura, T., Tomita, Y., Hirai, R., Yamaoka, K., Kaji, K. and Ichihara, A. (1985). Inhibitory effect of transforming growth factor-ß on’DNA synthesis of adult rat hepatocytes in primary culture, Biochem. Biophys. Res. Commun., Vol. 133, pp. 1042–1050.

    Article  PubMed  CAS  Google Scholar 

  26. Ignotz, R.A. and Massague, J. (1986). Transforming growth factor-b stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix., J. Bio. Chem. Vol. 261, pp. 4337–4345.

    CAS  Google Scholar 

  27. Weiner, F.R., Giambrone, M.-A., Czaja, M.J., Shah, A., Annoni, G., Takahashi, S., Eghbali, M. and Zem, M.A. (1990). Hepatology, Vol. 11, pp. 11–117.

    Article  Google Scholar 

  28. Matsumoto, K., Tajima, H., Okazaki, H. and Nakamura, T. (1992). Negative regulation of hepatocyte growth factor gene expression in human lung fibroblasts and leukemic cells by transforming growth factor-ß 1 and glucocorticoids, J. Biol. Chem., Vol. 267, pp. 24917–24920.

    PubMed  CAS  Google Scholar 

  29. Tsubouchi, H., Niitani, Y., Hirono, S., Nakayama, H., Gohda, E., Arakaki, N., Sakiyama, O., Takahashi, K., Kimoto, M., Kawakami, S., Setoguchi, M., Shin, S., Arima, T. and Daikuhara, Y. (1991): Levels of the human hepatocyte growth factor in serum of patients with various liver diseases determined by.enzyme-linked immunosorbent assay. Hepatology, Vol. 13, pp. 1–5.

    Article  PubMed  CAS  Google Scholar 

  30. Shiota, G., Okano, J., Kawasaki, H., Kawamoto. T. and Nakamura, T. (1995). Serum hepatocyte growth factor levels in liver diseases: Clinical implications, Hepatology, Vol,. 21, pp. 106–112.

    CAS  Google Scholar 

  31. Nagaike, M., Hirao, S., Tajima, H., Noji, S., Taniguchi, S.L, Matsumoto, K. and Nakamura, T. (1991). Renotropic functions of hepatocyte growth factor in renal regeneration after unilateral nephrectomy, J. Biol. Chem., Vol. 266, pp. 2278122784.

    Google Scholar 

  32. Kawaida, K., Matsumoto, K., Shimazu, H. and Nakamura. T. (1994). Hepatocyte growth factor prevents acute renal failure and accelerates renal regeneration, Proc. Natl. Acad. Sci. USA, Vol. 91, pp. 4357–4361.

    Article  PubMed  CAS  Google Scholar 

  33. Yanagita, K., Matsumoto, K., Sekiguchi, K., Ishibashi, H., Niho, Y. and Nakamura, T. (1993). Hepatocyte growth factor may act as a pulmotrophic factor on lung regeneration after acute lung injury. J. Biol. Chem., Vol. 268, pp. 21212–21217.

    PubMed  CAS  Google Scholar 

  34. Ohmichi, H., Matsumoto, K., and Nakamura, T. (1996). In vitro mitogenic action of HGF on lung epithelial cells: pulmotrophic role in lung regeneration, J. Am. Physiol., Vol. 270, pp. L 1031–1039.

    Google Scholar 

  35. Matsumoto K., Nakamura T. (1994). Hepatotrophic and renotrophic activities of HGF in vivo: Possible application of HGF for hepatic and renal disease, In “Liver Carcinogenesis: The Molecular Pathways”, NATO ASI Series, Springer-Verlag, pp. 436–448.

    Google Scholar 

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© 1997 Springer-Verlag Berlin Heidelberg

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Koshimizu, U., Matsumoto, K., Nakamura, T. (1997). Hepatotrophic Activities of HGF in Liver Regeneration after Injury and the Clinical Potentiality for Liver Diseases. In: Rana, S.V.S., Taketa, K. (eds) Liver and Environmental Xenobiotics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-12385-0_16

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  • DOI: https://doi.org/10.1007/978-3-662-12385-0_16

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  • Print ISBN: 978-3-662-12387-4

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