Abstract
Liver growth has fascinated scientists for many years, perhaps even centuries. Liver has a strong regenerative potential in response to toxic agents causing loss of hepatic parenchyma. Many chemical agents tested for carcinogenicity lead to formation of hepatic tumors. Other xenobiotic agents (e.g. anti-epileptics, hypolipidemic agents, barbiturates etc.) lead to a controlled expansion of hepatic mass above normal. Liver mass is gradually restored to normal upon discontinuation of the chemical, in a process accompanied by massive apoptosis. These and other phenomena have intensified interest in molecular mechanisms that control liver growth. The introduction of 2/3 partial hepatectomy as a systematic model for the study of liver regeneration in rats as shown by Higgins and Anderson (1931) led to a definition of phenomena related to liver regeneration which were well reproduced and became the guiding lines for research in the years that followed.
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References
Bisseil DM, Hammaker LE, Meyer UA. (1973) Parenchymal cells from adult rat liver in nonproliferating monolayer culture. I. Functional studies. J Cell Biol 59:722–734
Bucher NLR (1982) Thirty Years of Liver Regeneration: A distillate. In Cold Spring Harbor Conferences on Cell Proliferation, vol. 9 (Growth of cell in chemically defined media), p15–26
Crookston KP, Webb DJ, Lamarre J, Gonias SL.(1993).Binding of platelet-derived growth factor-BB and transforming growth factor-beta 1 to alpha 2-macroglobulin in vitro and in vivo: comparison of receptor-recognized and non-recognized alpha 2-macroglobulin conformations. Biochem J 293:443–450.
de Hemptinne, B Lorge, Kestens PJ and Lambotte L (1985) Hepatocellular hyperpolarizing factors and regeneration after partial hepatectomy in the rat. Acta Gastroenterol Belg 48: 424–431
DuBois RD (1990) Early changes in gene expression during liver regeneration: what do they mean? Hepatology 6:1079–1082
Fisher B, Szuch P, Levine M, Fisher ER (1971) A portal blood factor as the humoral agent in liver regeneration. Science 171: 575–577
Francavilla A, Starzl TE, Porter K, Foglieni CS, Michalopoulos GK, Carrieri G, Trejo Azzarone A, Barone M, Zeng QH (1991) Screening for candidate hepatic growth factors by selective portal infusion after canine Eck’s fistula. Hepatology 14:665–70.
Grisham JW (1962) A morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating liver; autoradiography with thymidine-H3. Cancer Res 22: 842–849
Grisham JW, Leong GF, Hole BV (1964) Heterotopic partial autotransplantation of rat liver. Technique and demonstration of structure and function of the graft. Cancer Res 24: 1474–1482
Higgins GM, and Anderson RM (1931) Experimental pathology of the liver: I. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12: 186–202
Jirtle RL, Michalopoulos G (1982) Effects of partial hepatectomy on transplanted hepatocytes. Cancer Res 42: 3000–3004
Keski-Oja J, Lohi J, Tuuttila A, Tryggvason K, Vartio T (1993) Proteolytic processing of the 72,000-Da type IV collagenase by urokinase plasminogen activator. Exp Cell Res 202:471–476
Kinoshita T, Hirao S, Matsumoto K, Nakamura T (1991) Possible endocrine control by hepatocyte growth factor of liver regeneration after partial hepatectomy. Biochem Biophys Res Commun 177:330–335.
Kuwashima Y, Aoki K, Kohyyama K, Ishikawa T. (1990) Hepatocyte Regeneration after partial hepatectomy occurs even under several thrombocytopenic conditions in the rat. Jpn. J. Cancer Res 81:607–612.
Lindroos P, Michalopoulos GK (1993) Response of phenobarbital- and ciprofibrate-exposed hepatocytes to growth factors in type I collagen gels. Carcinogenesis, 14:731–735
Lindroos P, Tsai WH, Zarnegar R, Michalopoulos GK (1992) Plasma levels of HGF in rats treated with tumor promoters. Carcinogenesis 13:139–141
Lindroos PM, Zarnegar R, Michalopoulos GK. (1991) Hepatic Growth Factor (Hepatopoietin A) Rapidly Increases in Plasma Prior to DNA Synthesis and Liver Regeneration Stimulated by Partial Hepatectomy and CCl4 Administration. Hepatology 13:743–750.
Liu KX, Kato Y, Narukawa M, Kim DC, Hanano M, Higuchi O, Nakamura T, Sugiyama Y. (1992) Importance of the liver in plasma clearance of hepatocyte growth factors in rats. Am J Physiol 263:G642–9.
Liu M, Michalopoulos G (1994) Ehancement of DNA synthesis stimulated by HGF in normal livers after infusion of Collagenase. Hepatology, In Press.
Liu Y, Michalopoulos GK, Zarnegar R. (1994) Structural and functional characterization of the mouse hepatocyte growth factor gene promoter. J Biol Chem 269:4152–4160
Lokker NA, Mark MR, Luis EA, Bennett GL, Robbins KA, Baker JB, Godowski PJ (1992) Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding. EMBO J 11:2503–2510.
Mars W, Zarnegar R, Michalopoulos G. (1993) Activation of Hepatocyte Growth Factor by the plasminogen activators uPA and tPA. Amer J Path 143:949–958.
Marsman DS, Goldsworthy TL, Popp JA (1992) Contrasting hepatocytic peroxisome proliferation, lipofuscin accumulation and cell turnover for the hepatocarcinogens Wy-14,643 and clofibric acid. Carcinogenesis 13:1011–1017
Masumoto A, Yamamoto N (1991) Sequestration of a hepatocyte growth factor in extracellular matrix in normal adult rat liver. Biochem Biophys Res Commun 174:90–95
Matsumoto K, Nakamura T (1993) Roles of HGF as a pleiotropic factor in organ regeneration. Experientia Supplementa 65:225–249
Matsumoto K, Okazaki H, Nakamura T (1992) Up-regulation of hepatocyte growth factor gene expression by interleukin-1 in human skin fibroblasts. Biochem Biophys Res Commun 188:235–243
Matsumoto K, Tajima H, Hamanoue M, Kohno S, Kinoshita T, Nakamura T (1992) Identification and characterization of “injurin,” an inducer of expression of the gene for hepatocyte growth factor. Proc Natl Acad Sci USA 89:3800–3804.
Meyer SA, Jirtle RL (1989) Phenobarbital decreases hepatocyte EGF receptor expression independent of protein kinase C activation. Biochem Biophys Res Commun 158:652–659
Michalopoulos G, Houck KA, Dolan ML, Luetteke NC (1984) Control of hepatocyte proliferation by two serum factors. Cancer Res 44:4414–4419
Michalopoulos GK, Appasamy R. (1993) Metabolism of HGF-SF and its role in liver regeneration. Experientia Supplementa 65:275–83.
Michalopoulos G, Bowen, W, Becich M, Howard TA (1993) Comparative analysis of mitogenic and morphogenic effects of HGF and EGF on rat and human hepatocytes maintained in collagen gels. J Cell Physiol 156:443–452.
Michalopoulos G, Bowen W, Mars W, Jirtle RL, Unpublished observations.
Michalopoulos GK, Eckl PM, Cruise JL, Novicki DL, Jirtle RL (1987) Mechanisms of rodent liver carcinogenesis. Toxicol Ind Health 3:119–128
Mizuno K, Takehara T, Nakamura T (1992) Proteolytic activation of a single-chain precursor of hepatocyte growth factor by extracellular serine-protease. Biochem Biophys Res Commun 189:1631–1638
Naka D, Ishii T, Yoshiyama Y, Miyazawa K, Hara H, Hishida T, Kidamura N (1992) Activation of hepatocyte growth factor by proteolytic conversion of a single chain form to a heterodimer. J Biol Chem 267:20114–20119
Naldini L, Tamagnone L, Vigna E, Sachs M, Hartmann G, Birchmeier W, Daikuhara Y, Tsubouchi H, Blasi F, Comoglio PM (1992) Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor. EMBO J 11:4825–4833.
Rabes HM, Wirsching R., Tuczek HV, Iseler G (1976) Analysis of cell cycle compartments of hepatocytes after partial hepatectomy. Cell Tissue Kinet 6: 517–532
Rao MS Subbarao V (1986) DNA synthesis in exocrine and endocrine pancreas after partial hepatectomy in Syrian golden hamsters. Experientia 42:833–834
Rifkin DB (1992) Plasminogen activator expression and matrix degradation. Matrix Suppl 1:20–22.
Roesel J, Rigsby D, Bailey A, Alvarez R, Sanchez JD, Campbell K, Shrestha K, Miller DM. (1989) Stimulation of protooncogene expression by partial hepatectomy is not tissue specific. Oncogene Research 5:129–136
Schirmacher P, Geerts A, Pietrangelo A, Dienes HP, Rogler CE. (1992) Hepatocyte growth factor/hepatopoietin A is expressed in fat-storing cells from rat liver but not myofibroblast-like cells derived from fat-storing cells. Hepatology 15:5–11.
Tomiya T, Tani M, Yamada S, Hayashi S, Umeda N, Fujiwara K. (1992) Serum hepatocyte growth factor levels in hepatectomized and nonhepatectomized surgical patients. Gastroenterology 103:1621–1624.
Tsai WH, Michalopoulos GK (1991) Responsiveness of hepatocytes to epidermal growth factor, transforming growth factor-beta and norepinephrine during treatment with xenobiotic hepatic tumor promoters. Cancer Lett 57:83–90
Tsai WH, Zarnegar R, Michalopoulos GK (1991) Long-term treatment with hepatic tumor promoters inhibits mitogenic responses of hepatocytes to acidic fibroblast growth factor and hepatocyte growth factor. Cancer Lett 59:103–108
Wada N, Marsman DS, Popp JA (1992) Dose-related effects of the hepatocarcinogen, Wy-14,643, on peroxisomes and cell replication. Fundam Appl Toxicol 18:149–154
Webber EM, Godowski PJ, Fausto N (1994) In vivo response of hepatocytes to growth factors requires an initial priming stimulus. Hepatology 489–497
Wolf HK, Zarnegar R, Michalopoulos GK (1991) Localization of Hepatocyte Growth Factor in human and rat tissues: An immunohistochemical study. Hepatology 14:488–494.
Yager JD, Zurlo J, Ni N (1991) Sex hormones and tumor promotion in liver. Proc Soc Exp Biol Med 198:667–674
Zarnegar R, DeFrances MC, Kost DP, Lindroos P, Michalopous GK (1991) Expression of hepatocyte growth factor mRNA in regenerating rat liver after partial hepatectomy. Biochem Biophys Res Commun 177:559–565.
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© 1994 Springer-Verlag Berlin Heidelberg
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Michalopoulos, G.K. (1994). HGF and Liver Growth Regulation. In: Skouteris, G.G. (eds) Liver Carcinogenesis. NATO ASI Series, vol 88. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79215-1_2
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DOI: https://doi.org/10.1007/978-3-642-79215-1_2
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-79217-5
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