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Mechanisms of Regulation of Liver Regeneration

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Artificial Liver Support

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Abstract

It is well known that liver growth and size are precisely regulated both in human and animals [3, 17]. The best experimental system for the analysis of these regulatory mechanisms is the compensatory growth of the liver (liver regeneration) that occurs after partial hepatectomy in rats or mice. An almost exact human counterpart for this experimental system now exists, as shown by studies of the regulation of the size and growth of transplanted human livers [32]. It appears that both in human and animals liver functional deficiencies relative to body demands can trigger cell proliferation in the normally quiescent adult liver. However, other studies have indicated that hepatic growth is at least in part regulated by the liver itself through circuits and mediators operating within the hepatic tissue. Thus, it is likely that functional demands in the liver or perhaps the metabolic adaptations set in motion in the liver in response to these demands activate hepatic growth regulatory circuits that lead to hepatocyte proliferation.

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References

  1. Braun L, Mead JE, Panzica M, Mikumo R, Bell GI, Fausto N (1988) Transforming growth factor P mRNA increases during liver regeneration: a possible paracrine mechanism of growth regulation. Proc Natl Acad Sci USA 85: 1539–1543

    Article  PubMed  CAS  Google Scholar 

  2. Bohman D, Bos JT, Admon A, Nishimura T, Vogt PT, Tjian R (1987) Human protooncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science 238: 1386–1392

    Article  Google Scholar 

  3. Bucher NLR, Malt RA (1971) Regeneration of liver and kidney. Little Brown, Boston, pp. 17–176

    Google Scholar 

  4. Carr BI, Hayashi I, Branum EL, Moses HL (1986) Inhibition of DNA synthesis in rat hepatocytes by platelet-derived type (3 transforming growth factor. Cancer Res 46: 2330–2334

    PubMed  CAS  Google Scholar 

  5. Coffey RJ Jr, Derynck R, Wilcox JN, Bringman Ts, Goustin As, Moses HL, Pittelkow MR (1987) Production and auto-induction of transforming growth factor a in human keratinocytes. Nature 328: 817–820

    Article  PubMed  CAS  Google Scholar 

  6. Derynck R (1988) Transforming growth factor a. Cell 54: 593–59523.

    Article  PubMed  CAS  Google Scholar 

  7. Earp HS, O’Keefe EJO (1981) Epidermal growth factor receptor number decreases during rat liver regeneration. J Clin Invest 67: 1580–1583

    Article  PubMed  CAS  Google Scholar 

  8. Fausto N, Mead JE (1989) Regulation of liver growth: protooncogenes and transforming growth factors. Lab Invest 60: 4–13

    PubMed  CAS  Google Scholar 

  9. Fausto N, Mead JE, Braun L, Thompson NL, Panzica M, Goyette M, Bell GI, Shank PR (1987) Proto-oncogene expression and growth factors during liver regeneration. Symp Fundam Cancer Res 39: 69–86

    CAS  Google Scholar 

  10. Fleig WE (1988) Liver-specific growth factors. Scand J Gastroenterol 238 (suppl 151): 31–36

    Article  Google Scholar 

  11. Francavilla A, Ove P, Polimeno L, Coetzee M, Makowka L, Rose J, Van Thiel DH, Starzl TE (1987) Extraction and partial purification of a hepatic stimulatory substance in rats, mice and dogs. Cancer Res 47: 5600–5605

    PubMed  CAS  Google Scholar 

  12. Gohda E, Tsubouchi H, Nakayama H, Hirono S, Takahashi K, Koura M, Hashimoto M, Daikuhara Y (1986) Human hepatocyte growth factor in plasma from patients with hepatic failure. Exp Cell Res 166: 139–159

    Article  PubMed  CAS  Google Scholar 

  13. Goustin AS, Leof EB, Shipley GD, Moses HL (1986) Growth factors and cancer. Cancer Res 46: 1015–1029

    PubMed  CAS  Google Scholar 

  14. Greenberg M, Ziff EB (1984) Stimulation of 3T3 cells induces transcription of the c-fos protooncogene. Nature 311: 433–437

    Article  PubMed  CAS  Google Scholar 

  15. Grisham JW (1962) Morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating rat liver: autoradiography with thymidine H3. Cancer Res 22: 842–849

    PubMed  CAS  Google Scholar 

  16. Guguen-Guillouzo C (1985) Role of homotypic and heterotypic cell interactions in expression of specific functions by cultured hepatocytes. In: Guillouzo A, Guguen-Guillouzo C (eds) Research in isolated cultured hepatocytes. Libbey, London, pp. 259–283

    Google Scholar 

  17. Higgins GM, Anderson RM (1931) Experimental pathology of the liver: I. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol Lab Med 12: 186–202

    Google Scholar 

  18. Karran S, Eagles C (1979) Regeneration. Part 1. Physical aspects. In: Wright R, Alberti KGMM, Karran S, Millward-Sadler GH (eds) Liver and biliary disease. Saunders, London, pp. 179–210

    Google Scholar 

  19. LaBrecque DR, Steele G, Fogerty S, Wilson M, Barton J (1987) Purification and physical-chemical characterization of hepatic stimulator substance. Hepatology 7: 100–106

    Article  PubMed  CAS  Google Scholar 

  20. Makino R, Hayashi K, Sugimura T (1984) C-myc transcript is induced in rat liver at very early stage of regeneration or by cycloheximide treatment. Nature 310: 697–698

    Article  PubMed  CAS  Google Scholar 

  21. McMahon JB, Richards WL, delCampo AA, Song M-KH, Thorgeirsson SS (1985) Differential effects of transforming growth factor ß on proliferation of normal and malignant rat liver epithelial cells in culture. Cancer Res 46: 4665–4671

    Google Scholar 

  22. Mead JE, Fausto N (1989) Transforming growth factor a may be a physiological regulator of liver regeneration by means of an autocrine mechanism. Proc Natl Acad Sei USA 86: 1558–1562

    Article  CAS  Google Scholar 

  23. Morello D, Fitzgerald MJ, Babinet C, Fausto N (1990) C-myc, c-fos, and c-jun regulation in the regenerating livers of normal and H-2K/c-myc transgenic mice. Mol Cell Biol 10: 3185–3193

    PubMed  CAS  Google Scholar 

  24. Nakamura N, Teramoto H, Ichihara A (1986) Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures. Proc Natl Acad Sei USA 83: 6489–6493

    Article  CAS  Google Scholar 

  25. Nakamura T, Tomita Y, Hirai T, Yamaoka K, Kaji K, Ichihara A (1985) Inhibitory effect of transforming growth factor ß on DNA synthesis of adult rat hepatocytes in primary culture. Biochem Biophys Res Commun 133: 1041–1050

    Article  Google Scholar 

  26. Reid LM, Narita M, Michiyasu F, Murray Z, Liverpool G, Rosenberg L (1986) Matrix and hormonal regulation of differentiation in liver cultures. In: Guillouzo A, Guguen-Guillouzo CB (eds) Research in isolated and cultured hepatocytes. Libbey, London, pp. 225–258

    Google Scholar 

  27. Roberts AB, Sporn MB (1985) Transforming growth factors. Cancer Surv 4: 683–705

    PubMed  CAS  Google Scholar 

  28. Rojkind M, Greenwel P (1988) The liver as a bioecological system. In: Arias IM, Jakoby WB, Popper H, Schachter D, Schafritz DA (eds) The liver: biology and pathology. Raven, New York, pp. 1269–1285

    Google Scholar 

  29. Russell WE, Coffey RJ, Ouellette AJ, Moses HL (1988) Type ß transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat. Proc Natl Acad Sci USA 85: 5126–5130

    Article  PubMed  CAS  Google Scholar 

  30. Sporn MB, Roberts AB (eds) (1990) The transforming growth factors ß. In: Peptide growth factors and their receptors. Springer, Berlin Heidelberg New York. (Handbook of Experimental Pharmacology, vol 95 )

    Google Scholar 

  31. Sporn MB, Todaro GJ (1980) Autocrine secretion and malignant transformation of cells. N Engl J Med 303: 878 - 880

    Article  PubMed  CAS  Google Scholar 

  32. Teixido J, Gilmore R, Lee DC, Massague J (1987) Integral membrane glycoprotein properties of the prohormone pro-transforming growth factor a. Nature 326: 883–885

    Article  PubMed  CAS  Google Scholar 

  33. Thompson NL, Mead JE, Braun L, Goyette M, Shank PR, Fausto N (1986) Sequential protooncogene expression during rat liver regeneration. Cancer Res 46: 3111–3117

    PubMed  CAS  Google Scholar 

  34. Van Thiel DH, Gavaler JS, Kam I, Francavilla A, Polimeno L, Schade PR, Smith J, Diven W, Penkrot RJ, Starzl TE (1989) Rapid growth of an intact human liver transplanted into a recipient larger than the donor. Gastroenterol 93: 1414–1419

    Google Scholar 

  35. Varmus H (1987) Cellular and viral oncogenes. In: Stamatoyannopoulos, Nienhuis AW, Leder P, Majerus PW (eds) The molecular basis of blood disease. Saunders, Philadelphia, pp. 271–346

    Google Scholar 

  36. Weinberg RA (1989) Oncogenes, antioncogenes and the molecular basis of multistep carcinogenesis. Cancer Res 49: 3713–3721

    PubMed  CAS  Google Scholar 

  37. Zarnegar R, Michalopoulos G (1989) Purification and biological characterization of human hepatopoietin A, a polypeptide growth factor for hepatocytes. Cancer Res 49: 3314–3320

    PubMed  CAS  Google Scholar 

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Authors
  1. N. Fausto
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Editors and Affiliations

  1. Abteilung für Gastroenterologie und Hepatologie, Medizinische Hochschule Hannover Krankenhaus Oststadt, Podbielskistraße 380, W-3000, Hannover 51, Germany

    G. Brunner

  2. Second Department of Surgery, Asahikawa Medical College Nishi-Kagura, Asahikawa, 078, Hokkaido, Japan

    M. Mito

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© 1992 Springer-Verlag Berlin Heidelberg

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Fausto, N. (1992). Mechanisms of Regulation of Liver Regeneration. In: Brunner, G., Mito, M. (eds) Artificial Liver Support. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77359-4_5

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  • DOI: https://doi.org/10.1007/978-3-642-77359-4_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-77361-7

  • Online ISBN: 978-3-642-77359-4

  • eBook Packages: Springer Book Archive

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