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Mechanisms determining phenotypic heterogeneity of hepatocytes

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Abstract

This review summarizes results of biochemical and immunohistochemical studies indicating the existence of functional heterogeneity of hepatocytes depending on their localization in the hepatic acinus; this determines characteristic features of metabolism of carbohydrates, lipids, and xenobiotics. The physiological significance of hepatocyte heterogeneity is discussed. According to the proposed model of intercellular communication, the metabolic specialization of hepatocytes is determined by secretory activity of hepatic resident macrophages (Kupffer cells) localized mainly in the periportal zone of the liver acinus. Macrophages participate in secretion of a wide spectrum of intercellular mediators (cytokines, prostaglandins, growth factors) and also in metabolism of numerous blood metabolites and biologically active substances (hormones, lipoproteins, etc.). In the sinusoid and in the space of Disse (also known as perisinusoidal space) they form a concentration gradient of regulatory factors and metabolites inducing the phenotypic differences between hepatocytes.

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Abbreviations

apo:

apolipoprotein

CYP:

cytochrome P450

EGF:

epidermal growth factor

G6PDH:

glucose-6-phosphate dehydrogenase

HDL:

high density lipoproteins

HGF:

hepatocyte growth factor

IGF:

insulin-like growth factor

IGFBP:

insulin-like growth factor binding protein

IL:

interleukin

LAP:

latency associated peptide

LDL:

low density lipoproteins

LTBP:

latent TGF-binding protein

MCT:

3-methylcholanthrene

PAI-1:

plasminogen activator inhibitor-1

PB:

phenobarbital

PEPCK:

phosphoenolpyruvate carboxykinase

TGF-β1:

transforming growth factor-β1

TNF-α:

tumor necrosis factor-α

VLDL:

very low density lipoproteins

References

  1. Wilson, J. W. (1958) in Liver Function, a Symposium on Approaches to the Quantitative Description of Liver Function, American Institute of Biological Sciences, Washington, DC, pp. 175–197.

    Google Scholar 

  2. Jungermann, K. (1995) Histochem. Cell Biol., 103, 81–91.

    Article  PubMed  CAS  Google Scholar 

  3. Katz, N. (1992) J. Nutr., 122, 843–849.

    PubMed  CAS  Google Scholar 

  4. Bengtsson, B. G., Smith-Killand, A., and Morland, J. (1984) Exp. Mol. Pathol., 41, 44–57.

    Article  PubMed  CAS  Google Scholar 

  5. Panin, L. E., and Usynin, I. F. (1986) Byul. Eksp. Biol. Med., No. 6, 695–697.

  6. Rappaport, A. M. (1975) in Diseases of the Liver (Schiff, L., ed.) pp. 1–50.

  7. Schmucker, B. L., Mooney, J. S., and Jones, A. L. (1978) J. Cell Biol., 78, 319–337.

    Article  PubMed  CAS  Google Scholar 

  8. Kanamura, S., Kanai, K., and Watanabe, J. (1990) J. Electron. Microsc. Tech., 14, 92–105.

    Article  PubMed  CAS  Google Scholar 

  9. Ferri, D., Moro, L., Mastrodonato, M., Capuano, F., Marra, E., Liquori, G. E., and Greco, M. (2005) J. Biol. Cell., 97, 277–288.

    Article  CAS  Google Scholar 

  10. Lindauer, M., Beier, K., Volkl, A., and Fahimi, H. D. (1994) Hepatology, 20, 475–486.

    PubMed  CAS  Google Scholar 

  11. Van Noorden, C. J., Vogels, I. M., and James, J. (1994) Hepatology, 20, 714–724.

    PubMed  CAS  Google Scholar 

  12. Layden, T. J., and Boyer, J. L. (1978) Lab. Invest., 39, 110–119.

    PubMed  CAS  Google Scholar 

  13. Blitzer, B. L., and Boyer, B. (1982) Gastroenterology, 82, 346–357.

    PubMed  CAS  Google Scholar 

  14. Castagna, M., and Chauveau, J. (1969) Exptl. Cell Res., 57, 211–222.

    Article  PubMed  CAS  Google Scholar 

  15. Wanson, J.-C., Drochmans, P., May, C., Penasse, W., and Popowski, A. (1975) J. Cell Biol., 66, 23–41.

    Article  PubMed  CAS  Google Scholar 

  16. Allen, C. M., and Paine, A. J. (1983) Biochem. Soc. Trans., 11, 275.

    Google Scholar 

  17. Baron, J., Redick, J. A., and Guengerich, P. P. (1982) J. Biol. Chem., 257, 953–957.

    PubMed  CAS  Google Scholar 

  18. Moody, D. E., Taylor, L. A., Smuckler, E. A., Levin, W., and Thomas, P. E. (1983) Drug Met. Dis., 11, 339–343.

    CAS  Google Scholar 

  19. Tavassoli, M., Ozols, J., Sugimoto, G., Cox, K. H., and Muller-Eberhard, U. (1976) Biochem. Biophys. Res. Commun., 72, 281–287.

    PubMed  CAS  Google Scholar 

  20. Panin, L. E., and Usynin, I. F. (1987) Byul. Eksp. Biol. Med., No. 2, 172–174.

  21. Tordjmann, T., Berthon, B., Lardeux, B., Moreau, A., Jacquemin, E., Combettes, L., Feldmann, G., and Claret, M. (1997) Hepatology, 26, 1592–1599.

    Article  PubMed  CAS  Google Scholar 

  22. Ugele, B., and Gebhardt, R. (2003) Hepatol. Res., 27, 238–247.

    Article  PubMed  CAS  Google Scholar 

  23. Fisher, W., Ick, M., and Katz, N. R. (1982) Hoppe-Seyler’s Z. Physiol. Chem., 363, 375–380.

    Google Scholar 

  24. Usynin, I. F. (1999) The Role of Macrophages in Regulation of Metabolic Processes in the Liver during Functional Load of the Body: Doctoral dissertation [in Russian], Novosibirsk.

  25. Wisse, E., Braet, F., Luo, D., Vermijlen, D., Eddouks, M., Konstandoulaki, M., Empsen, C., and de Zanger, R. B. (1999) in Liver Diseases and Hepatic Sinusoidal Cells (Tanikawa, K., and Ueno, T., eds.) Springer, Tokyo, pp. 17–55.

    Google Scholar 

  26. Usynin, I. F. (1987) Biochemical Analysis of Functional Heterogeneity of Hepatocytes: Candidate’s dissertation [in Russian], Novosibirsk.

  27. Ikezawa, Y., Yamatani, K., Ogawa, A., Ohnuma, H., Igarashi, M., Daimon, M., Manaka, H., and Sasaki, H. (1998) J. Lab. Clin. Med., 132, 547–555.

    Article  PubMed  CAS  Google Scholar 

  28. Giffin, B. F., Drake, R. L., Morris, R. E., and Cardell, R. R. (1993) J. Histochem. Cytochem., 41, 1849–1862.

    PubMed  CAS  Google Scholar 

  29. Sasse, D., and Hoffmann, H. (1982) Histochemistry, 75, 31–42.

    Article  PubMed  CAS  Google Scholar 

  30. Asada-Kubota, M., Kanai, K., and Kanamura, S. (1982) Anat. Rec., 202, 395–405.

    Article  PubMed  CAS  Google Scholar 

  31. Quistorff, B., Katz, N., and Witters, L. A. (1992) Enzyme, 46, 59–71.

    PubMed  CAS  Google Scholar 

  32. Rieder, H. (1981) Histochemistry, 72, 579–615.

    Article  PubMed  CAS  Google Scholar 

  33. Aspichueta, P., Perez, S., Ochoa, B., and Fresnedo, O. (2005) J. Lipid Res., 46, 1017–1026.

    Article  PubMed  CAS  Google Scholar 

  34. Panin, L. E., Usynin, I. F., and Polyakov, L. M. (1986) Vopr. Med. Khim., No. 4, 106–110.

  35. Botham, K. M., Fresnedo, O., Romero, J. R., and Ochoa, B. (1998) Gen. Physiol. Biophys., 17, 79–94.

    PubMed  CAS  Google Scholar 

  36. Voorschuur, A. H., Kuiper, J., Neelissen, J. A., Boers, W., and van Berkel, T. J. (1994) Biochem. J., 303, 809–816.

    PubMed  CAS  Google Scholar 

  37. Romero, J. R., Fresnedo, O., Isusi, E., Barrionuevo, J., and Ochoa, B. (1999) Lipids, 34, 907–913.

    Article  PubMed  CAS  Google Scholar 

  38. Gebhardt, R., Alber, J., Wegner, H., and Mecke, D. (1994) Biochem. Pharmacol., 48, 761–766.

    Article  PubMed  CAS  Google Scholar 

  39. McKinnon, R. A., Hall, P. D., Quattrochi, L. C., Tukey, R. H., and McManus, M. E. (1991) Hepatology, 14, 848–856.

    Article  PubMed  CAS  Google Scholar 

  40. Taira, Y., Redick, J. A., and Baron, J. (1980) Mol. Pharmacol., 17, 374–381.

    PubMed  CAS  Google Scholar 

  41. Thurman, R. G., and Kauffman, B. C. (1985) Hepatology, 5, 144–151.

    Article  PubMed  CAS  Google Scholar 

  42. Ekberg, K., Chandramouli, V., Kumaran, K., Schumann, W. C., Wahren, J., and Landau, B. R. (1995) J. Biol. Chem., 270, 21715–21717.

    Article  PubMed  CAS  Google Scholar 

  43. Ullrich, D., Fischer, G., Katz, H., and Bock, K. W. (1984) Chem.-Biol. Interact., 48, 181–190.

    Article  PubMed  CAS  Google Scholar 

  44. Novikoff, A. B. (1959) J. Histochem. Cytochem., 7, 240–244.

    PubMed  CAS  Google Scholar 

  45. Allen, J. W., Khetani, S. R., and Bhatia, S. N. (2005) Toxicol. Sci., 84, 110–119.

    Article  PubMed  CAS  Google Scholar 

  46. Jungermann, K., and Kietzmann, T. (2000) Hepatology, 31, 255–260.

    Article  PubMed  CAS  Google Scholar 

  47. Gulak, P. V., Dudchenko, A. M., Zaitsev, V. V., Luk’yanova, L. D., Novikov, K. N., Orlov, S. N., Pokudin, N. I., Popova, O. A., and Ugolev, A. T. (1985) Hepatocyte: Functional and Metabolic Properties [in Russian], Nauka, Moscow.

    Google Scholar 

  48. Gebhardt, R., and Mecke, D. (1984) in Glutamate Metabolism in Mammalian Tissues (Haussinger, D., and Sies, H., eds.) Springer Verlag, Heidelberg, pp. 98–121.

    Google Scholar 

  49. Stoll, B., McNelly, S., Buscher, H. P., and Haussinger, D. (1991) Hepatology, 13, 247–253.

    PubMed  CAS  Google Scholar 

  50. Wilson, D. F., Owen, C. S., and Erecinska, M. (1979) Arch. Biochem. Biophys., 195, 494–504.

    Article  PubMed  CAS  Google Scholar 

  51. Ghosh, A. K., Finegold, D., White, W., Zawalich, K., and Matschinsky, F. N. (1982) J. Biol. Chem., 257, 5476–5481.

    PubMed  CAS  Google Scholar 

  52. Jungermann, K., and Katz, N. (1982) in Metabolic Compartmentation, Academic Press, London, pp. 411–435.

    Google Scholar 

  53. Rossouw, J. E., Labadarios, D., Vinik, I., and de Villiers, A. S. (1978) Metabolism, 27, 1067–1073.

    Article  PubMed  CAS  Google Scholar 

  54. Wittig, B., Zierz, S., Gubernatis, G., Nath, A., and Jungermann, K. (1985) Biol. Chem. Hoppe-Seyler, 366, 713–722.

    PubMed  CAS  Google Scholar 

  55. Miethke, H., Wittig, B., Nath, A., Zierz, S., and Jungermann, K. (1985) Biol. Chem. Hoppe-Seyler, 366, 493–501.

    PubMed  CAS  Google Scholar 

  56. Lee, S. M., and Clemens, M. G. (2004) Shock, 22, 82–87.

    Article  PubMed  CAS  Google Scholar 

  57. Bouwens, L., de Bleser, P., Vanderkerken, K., Geerts, B., and Wisse, E. (1992) Enzyme, 46, 155–168.

    PubMed  CAS  Google Scholar 

  58. Shin, Y. C. (1997) Anat. Rec., 247, 206–213.

    Article  PubMed  CAS  Google Scholar 

  59. Bykov, B., Ylipaasto, P., Eerola, L., and Lindros, K. O. (2003) Scand. J. Gastroenterol., 38, 1256–1261.

    Article  PubMed  CAS  Google Scholar 

  60. Naito, M., Hasegawa, G., Ebe, Y., and Yamamoto, T. (2004) Med. Electron. Microsc., 37, 16–28.

    Article  PubMed  CAS  Google Scholar 

  61. Ogi, M., Yokomori, H., Oda, M., Yoshimura, K., Nomura, M., Ohshima, S., Akita, M., Toda, K., and Ishii, H. (2003) Med. Electron. Microsc., 36, 33–40.

    Article  PubMed  CAS  Google Scholar 

  62. Theuerkauf, I., Zhou, H., and Fischer, H. P. (2001) Virchows Arch., 438, 498–504.

    Article  PubMed  CAS  Google Scholar 

  63. Pusztaszeri, M. P., Seelentag, W., and Bosman, F. T. (2006) J. Histochem. Cytochem., 54, 385–395.

    Article  PubMed  CAS  Google Scholar 

  64. Dini, L., and Carla, E. C. (1998) Exp. Cell Res., 240, 388–393.

    Article  PubMed  CAS  Google Scholar 

  65. Hailfinger, S., Jaworski, M., Braeuning, A., Buchmann, A., and Schwarz, M. (2006) Hepatology, 43, 407–414.

    Article  PubMed  CAS  Google Scholar 

  66. Braeuning, A., Ittrich, C., Kohle, C., Buchmann, A., and Schwarz, M. (2007) Drug Metab. Dispos., 35, 503–507.

    Article  PubMed  CAS  Google Scholar 

  67. Benhamouche, S., Decaens, T., Godard, C., Chambrey, R., Rickman, D. S., Moinard, C., Vasseur-Cognet, M., Kuo, C. J., Kahn, A., Perret, C., and Colnot, S. (2006) Dev. Cell, 10, 759–770.

    Article  PubMed  CAS  Google Scholar 

  68. Burke, Z. D., and Tosh, D. (2006) BioEssays, 28, 1072–1077.

    Article  PubMed  CAS  Google Scholar 

  69. Gumucio, J. J., and Gebhardt, R. (1992) Hepatology, 16, 843–845.

    Article  Google Scholar 

  70. Decker, K. (1990) Eur. J. Biochem., 192, 245–261.

    Article  PubMed  CAS  Google Scholar 

  71. Kmiec, Z. (2001) Adv. Anat. Embryol. Cell Biol., 161, 1–151.

    Google Scholar 

  72. Cavaillon, J. M. (1995) Bull. Inst. Pasteur, 93, 21–41.

    Article  CAS  Google Scholar 

  73. Berry, L. J., Goodrum, K. J., Resnick, I. G., and Ford, C. W. (1980) in RES and Pathogenesis of Liver Diseases (Liehr, H., and Grun, M., eds.) North Holland Biomedical Press, pp. 257–266.

  74. McCallum, R. E., Seale, T. W., and Stith, R. D. (1983) Infect. Immun., 39, 213–219.

    PubMed  CAS  Google Scholar 

  75. Hill, M., and McCallum, R. (1991) J. Clin. Invest., 88, 811–816.

    Article  PubMed  CAS  Google Scholar 

  76. Bernuau, D., Legres, L., Giuily, N., Fey, G., and Feldmann, G. (1989) J. Exp. Med., 170, 349–354.

    Article  PubMed  CAS  Google Scholar 

  77. Blumberg, D., Hochwald, S., Brennan, M. F., and Burt, M. (1995) Metabolism, 44, 145–146.

    Article  PubMed  CAS  Google Scholar 

  78. Thoresen, G. H., Refsnes, M., Dajani, O. F., Johansen, E. J., and Christoffersen, T. (1995) Pharmacol. Toxicol., 76, 163–170.

    PubMed  CAS  Google Scholar 

  79. Hill, M., and McCallum, R. E. (1992) Infect. Immun., 60, 4040–4050.

    PubMed  CAS  Google Scholar 

  80. Yerkovich, S. T., Rigby, P. J., Fournier, P. A., Olynyk, J. K., and Yeoh, G. C. (2004) Int. J. Biochem. Cell. Biol., 36, 1462–1472.

    PubMed  CAS  Google Scholar 

  81. Miyake, H., Takehara, H., and Starnes, F. J. (1994) Clin. Biochem. Nutr., 17, 1–9.

    CAS  Google Scholar 

  82. Christ, B., and Nath, A. (1996) Biochem. J., 320, 161–166.

    PubMed  CAS  Google Scholar 

  83. Hill, M. R., Stith, R. D., and McCallum R. E. (1986) J. Immunol., 137, 858–862.

    PubMed  CAS  Google Scholar 

  84. Kanemaki, T., Kitade, H., Kaibori, M., Sakitani, K., Hiramatsu, Y., Kamiyama, Y., Ito, S., and Okumura, T. (1998) Hepatology, 27, 1296–1303.

    Article  PubMed  CAS  Google Scholar 

  85. Sprangers, F., Sauerwein, H. P., Romijn, J. A., van Woerkom, G. M., and Meijer, A. J. (1998) Biochem. J., 330, 1045–1049.

    PubMed  CAS  Google Scholar 

  86. Christ, B., Nath, A., Heinrich, P. C., and Jungermann, K. (1994) Hepatology, 20, 1577–1583.

    Article  PubMed  CAS  Google Scholar 

  87. Kuiper, J., Casteleyn, E., and van Berkel, T. J. C. (1989) Agent. Action, 26, 201–202.

    Article  CAS  Google Scholar 

  88. Schieferdecker, H. L., Schlaf, G., Jungermann, K., and Gotze, O. (2001) Int. Immunopharmacol., 1, 469–481.

    Article  PubMed  CAS  Google Scholar 

  89. Pestel, S., Schlaf, G., Gotze, O., Jungermann, K., and Schieferdecker, H. L. (2003) Lab. Invest., 83, 1733–1741.

    Article  PubMed  CAS  Google Scholar 

  90. Okumura, T., and Saito, K. (1990) Prostaglandins, 39, 525–540.

    Article  PubMed  CAS  Google Scholar 

  91. Nukina, S., Fusaoka, T., and Thurman, R. G. (1994) Am. J. Physiol., 266, G99–G105.

    PubMed  CAS  Google Scholar 

  92. Hardardottir, I., Grunfeld, C., and Feingold, K. R. (1995) Biochem. Soc. Trans., 23, 1013–1018.

    PubMed  CAS  Google Scholar 

  93. Chajek-Shaul, T., Freidman, G., Stein, O., Etienne, J., and Stein, Y. (1989) Biochim. Biophys. Acta, 1001, 316–124.

    PubMed  CAS  Google Scholar 

  94. Feingold, K. R., Soued, M., Serio, M. K., Moser, A. N., Dinarello, C. A., and Grunfeld, C. (1989) Endocrinology, 125, 267–274.

    PubMed  CAS  Google Scholar 

  95. Grunfeld, C., Verdier, J. A., Neese, R., Moser, A. H., and Feingold, K. R. (1988) J. Lipid Res., 29, 1327–1335.

    PubMed  CAS  Google Scholar 

  96. Nonogaki, K., Fuller, G. M., Fuentes, N. L., Moser, A. H., Staprans, I., Grunfeld, C., and Feingold, K. R. (1995) Endocrinology, 136, 2143–2149.

    Article  PubMed  CAS  Google Scholar 

  97. Grove, R. I., Mazzucco, C., Allegretto, N., Kiener, P. A., Spitalny, G., Radka, S. F., Shoyab, M., Antonaccio, M., and Warr, G. A. (1991) J. Lipid Res., 32, 1889–1897.

    PubMed  CAS  Google Scholar 

  98. Liu, J. W., Grove, R. I., and Vestal, R. E. (1994) Cell Growth Differ., 5, 1333–1338.

    PubMed  CAS  Google Scholar 

  99. Rea, T. J., Bisgaier, C. L., Demattos, R. B., and Pape, M. E. (1994) J. Lipid Res., 35, 1274–1282.

    PubMed  CAS  Google Scholar 

  100. Ettinger, W. H., Varma, V. K., Sorcithomas, M., Parks, J. S., Sigmon, R. C., Smith, T. K., and Verdery, P. B. (1994) Arterioscler. Thromb., 14, 8–13.

    PubMed  CAS  Google Scholar 

  101. Ghezzi, P., Saccardo, B., and Bianchi, M. (1986) Biochem. Biophys. Res. Commun., 136, 316–321.

    Article  PubMed  CAS  Google Scholar 

  102. Craig, P. I., Williams, S. J., Cantrill, E., and Farrell, G. C. (1989) Gastroenterology, 197, 999–1004.

    Google Scholar 

  103. Morgan, E. T., Thomas, K. B., Swanson, R., Vales, T., Hwang, J., and Wright, K. (1994) Biochim. Biophys. Acta, 1219, 475–483.

    PubMed  CAS  Google Scholar 

  104. Cantoni, L., Carelli, M., Ghezzi, P., Delgado, R., Faggioni, R., and Rizzardini, M. (1995) Eur. J. Pharmacol. Environ. Toxic., 292, 257–263.

    Article  CAS  Google Scholar 

  105. Sunman, J. A., Hawke, R. L., LeCluyse, E. L., and Kashuba, A. D. B. (2004) Drug Metab. Dis., 32, 359–363.

    Article  CAS  Google Scholar 

  106. Abdel-Razzak, Z., Corcos, L., Fautrel, A., Campion, J. P., and Guillouzo, A. (1994) Mol. Pharmacol., 46, 1100–1110.

    PubMed  CAS  Google Scholar 

  107. Stadler, J., Trockfeld, J., Schmalix, W. A., Brill, T., Siewert, J. R., Greim, H., and Doehmer, J. (1994) Proc. Natl. Acad. Sci. USA, 91, 3559–3563.

    Article  PubMed  CAS  Google Scholar 

  108. Panin, L. E., Sokolova, M. V., and Usynin, I. F. (1991) Patol. Fiziol. Eksp. Ter., No. 1, 20–22.

  109. Mayanski, D. N., Wisse, E., and Decker, K. (1992) New Horizons of Hepatology [in Russian], Nauka, Novosibirsk.

    Google Scholar 

  110. Takeishi, T., Hirano, K., Kobayashi, T., Hasegawa, G., Hatakeyama, K., and Naito, M. (1999) Arch. Histol. Cytol., 62, 413–422.

    Article  PubMed  CAS  Google Scholar 

  111. Meijer, C., Wiezer, M. J., Diehl, A. M., Schouten, H. J., Schouten, H. J., Meijer, S., van Rooijen, N., van Lambalgen, A. A., Dijkstra, C. D., and van Leeuwen, P. A. (2000) Liver, 20, 66–77.

    Article  PubMed  CAS  Google Scholar 

  112. Malik, R., Selden, C., and Hodgson, H. (2002) Semin. Cell. Dev. Biol., 13, 425–431.

    Article  PubMed  CAS  Google Scholar 

  113. Fausto, N., and Riehle, K. J. (2005) J. Hepatobiliary Pancreat. Surg., 12, 181–189.

    Article  PubMed  Google Scholar 

  114. Satoh, M., and Yamazaki, M. (1992) J. Cell Physiol., 150, 134–139.

    Article  PubMed  CAS  Google Scholar 

  115. Fausto, N., Laird, A. D., and Webber, E. M. (1995) FASEB J., 9, 1527–1536.

    PubMed  CAS  Google Scholar 

  116. Diehl, A. M., and Rai, R. J. (1996) Gastroenterol. Hepatol., 11, 466–470.

    Article  CAS  Google Scholar 

  117. Rolfe, M., James, N. H., and Roberts, R. A. (1997) Carcinogenesis, 18, 2277–2280.

    Article  PubMed  CAS  Google Scholar 

  118. Iocca, H. A., and Isom, H. C. (2003) Am. J. Pathol., 163, 465–476.

    PubMed  CAS  Google Scholar 

  119. Abshagen, K., Eipel, C., Kalff, J. C., Menger, M. D., and Vollmar, B. (2007) Am. J. Physiol. Gastrointest. Liver Physiol., 292, G1570–G1577.

    Article  PubMed  CAS  Google Scholar 

  120. Yamada, Y., and Fausto, N. (1998) Am. J. Pathol., 152, 1577–1589.

    PubMed  CAS  Google Scholar 

  121. Blindenbacher, A., Wang, X., Langer, I., Savino, R., Terracciano, L., and Heim, M. H. (2003) Hepatology, 38, 674–682.

    Article  PubMed  CAS  Google Scholar 

  122. Galun, E., and Axelrod, J. H. (2002) Biochim. Biophys. Acta, 1592, 345–358.

    Article  PubMed  CAS  Google Scholar 

  123. Aldeguer, X., Debonera, F., Shaked, A., Krasinkas, A. M., Gelman, A. E., Que, X., Zamir, G. A., Hiroyasu, S., Kovalovich, K. K., Taub, R., and Olthoff, K. M. (2002) Hepatology, 35, 40–48.

    Article  PubMed  CAS  Google Scholar 

  124. Taub, R., Greenbaum, L. E., and Peng, Y. (1999) Semin. Liver Dis., 19, 117–127.

    PubMed  CAS  Google Scholar 

  125. Gohda, E. (2002) Nippon. Yakurigaku. Zasshi., 119, 287–294.

    PubMed  CAS  Google Scholar 

  126. Ogura, Y., Hamanoue, M., Tanabe, G., Mitsue, S., Yoshidome, S., Nuruki, K., and Aikou, T. (2001) Hepatogastroenterology, 48, 545–549.

    PubMed  CAS  Google Scholar 

  127. Noji, S., Tashiro, K., Koyama, E., Nohno, T., Ohyama, K., Taniguchi, S., and Nakamura, T. (1990) Biochem. Biophys. Res. Commun., 173, 42–47.

    Article  PubMed  CAS  Google Scholar 

  128. Hata, J., Ikeda, E., Uno, H., and Asano, S. (2002) J. Histochem. Cytochem., 50, 1461–1468.

    PubMed  CAS  Google Scholar 

  129. Takeishi, T., Hirano, K., Kobayashi, T., Hasegawa, G., Hatakeyama, K., and Naito, M. (1999) Arch. Histol. Cytol., 62, 413–422.

    Article  PubMed  CAS  Google Scholar 

  130. Iida, I., Johkura, K., Teng, R., Kubota, S., Cui, L., Zhao, X., Ogiwara, N., Okouchi, Y., Asanuma, K., Nakayama, J., and Sasaki, K. J. (2003) Histochem. Cytochem., 51, 1139–1149.

    CAS  Google Scholar 

  131. Pal’tsev, M. A., and Ivanov, A. A. (1995) Intercellular Interactions [in Russian], Meditsina, Moscow.

    Google Scholar 

  132. Kimura, M., and Ogihara, M. (1998) Eur. J. Pharmacol., 354, 271–281.

    Article  PubMed  CAS  Google Scholar 

  133. Scott, C. D., and Baxter, R. C. (1986) Endocrinology, 119, 2346–2352.

    Article  PubMed  CAS  Google Scholar 

  134. Pinzani, M., Abboud, H. E., and Aron, D. C. (1990) Endocrinology, 127, 2343–2349.

    PubMed  CAS  Google Scholar 

  135. Scharf, J., Ramadori, G., Braulke, T., and Hartmann, H. (1996) Hepatology, 23, 818–827.

    Article  PubMed  CAS  Google Scholar 

  136. Zimmermann, E. M., Li, L., Hoyt, E. C., Pucilowska, J. B., Lichtman, S., and Lund, P. K. (2000) Am. J. Physiol. Gastrointest. Liver Physiol., 278, G447–G457.

    PubMed  CAS  Google Scholar 

  137. Villafuerte, B. C., Koop, B. L., Pao, C.-I., Gu, L., Birdsong, G. G., and Phillips, L. S. (1994) Endocrinology, 134, 2044–2050.

    Article  PubMed  CAS  Google Scholar 

  138. Meyer, D. H., Bachem, M. G., and Gressner, A. M. (1991) FEBS Lett., 283, 150–154.

    Article  PubMed  CAS  Google Scholar 

  139. Kimura, M., and Ogihara, M. (1999) Eur. J. Pharmacol., 386, 271–277.

    Article  PubMed  CAS  Google Scholar 

  140. De Bleser, P. J., Niki, T., Rogiers, V., and Geerts, A. (1997) J. Hepatol., 26, 886–893.

    Article  PubMed  Google Scholar 

  141. Roth, S., Gong, W., and Gressner, A. M. (1998) J. Hepatol., 29, 915–922.

    Article  PubMed  CAS  Google Scholar 

  142. Breitkopf, K., Lahme, B., Tag, C. G., and Gressner, A. M. (2001) Hepatology, 33, 387–396.

    Article  PubMed  CAS  Google Scholar 

  143. George, S. J., Johnson, J. L., Smith, M. A., Angelini, G. D., and Jackson, C. L. (2005) J. Vasc. Res., 42, 247–254.

    Article  PubMed  CAS  Google Scholar 

  144. Gentry, J., Arthur, M. J., and Benyon, R. C. (1996) Hepatology, 24, 1172–1178.

    Article  PubMed  Google Scholar 

  145. Fearns, C., and Loskutoff, D. J. (1997) Am. J. Pathol., 150, 579–590.

    PubMed  CAS  Google Scholar 

  146. Panin, L. E., Sokolova, M. V., and Usynin, I. F. (1990) Tsitologiya, No. 5, 528–532.

  147. Usynin, I. F., Panin, L. E., Kharkovski, A. V., Gorjacheva, M. V., Ostanina, L. S., Trubitsina, O. M., and Tretjakova, T. A. (1995) in Cells of the Hepatic Sinusoid (Wisse, E., Knook, D. L., and Wake, K., eds.) Vol. 5, The Kupffer Cell Foundation, Leiden, The Netherlands, pp. 297–298.

    Google Scholar 

  148. Panin, L. E., Usynin, I. F., Kharkovski, A. V., Gorjacheva, M. V., and Maksimov, V. F. (1997) in Cells of the Hepatic Sinusoid (Wisse, E., Knook, D. L., and Balabaud, C., eds.) Vol. 6, The Kupffer Cell Foundation, Leiden, The Netherlands, pp. 156–157.

    Google Scholar 

  149. Panin, L. E., Maksimov, V. F., Korostyshevskaya, I. M., and Usynin, I. F. (2002) J. Steroid Biochem. Mol. Biol., 81, 69–76.

    Article  PubMed  CAS  Google Scholar 

  150. Usynin, I. F., Panin, L. E., Kharkovski, A. V., and Gorjacheva, M. V. (1995) Biochemistry (Moscow), 60, 399–406.

    Google Scholar 

  151. Miyazawa, M., Torii, T., Toshimitsu, Y., and Koyama, I. (2005) Transplant Proc., 37, 2398–2401.

    Article  PubMed  CAS  Google Scholar 

  152. Zinchenko, Y. S., Schrum, L. W., Clemens, M., and Coger, R. N. (2006) Tissue Eng., 12, 751–761.

    Article  PubMed  CAS  Google Scholar 

  153. Panin. L. E., Usynin, I. F., Trubytsyna, O. M., Kharkovski, A. V., Sokolova, M. V., and Ostanina, L. S. (1994) Biochemistry (Moscow), 59, 249–254.

    Google Scholar 

  154. Provatorov, G. V., Usynin, I. F., Polyakov, L. M., and Glazyrin, A. L. (1993) Tsytologiya, 35, 42–57.

    Google Scholar 

  155. Van Berkel, Th. J. C., Kruijt, J. K., van Gent, T., and van Tol, A. (1980) Biochem. Biophys. Res. Commun., 92, 1002–1008.

    Article  PubMed  Google Scholar 

  156. Panin. L. E., Usynin, I. F., Kharkovski, A. V., and Poteryaeva, O. N. (1998) Byul. Eksp. Biol. Med., No. 7, 43–45.

  157. Rahim, A. T. M. A., Miyazaki, A., Morino, Y., and Horiuchi, S. (1991) Biochim. Biophys. Acta, 1082, 195–203.

    PubMed  CAS  Google Scholar 

  158. Van Berkel, Th. J. C. (1979) Trends Biochem. Sci., 9, 202–205.

    Google Scholar 

  159. Favre, G., Blancy, E., Tournier, J. F., and Soula, G. (1989) Biochim. Biophys. Acta, 1013, 118–124.

    Article  PubMed  CAS  Google Scholar 

  160. Gospodarowicz, D., Massoglia, D. S., and Cheng, D. K. (1986) J. Cell Physiol., 127, 121–136.

    Article  PubMed  CAS  Google Scholar 

  161. Nofer, J. R., Junker, R., Pulawski, E., Fobker, M., Levkau, B., von Eckardstein, A., Seedorf, U., Assmann, G., and Walter, M. (2001) Thromb. Haemost., 85, 730–735.

    PubMed  CAS  Google Scholar 

  162. Favre, G., Tazi, K. A., Le Gaillard, F., Bennis, F., Hachem, H., and Soula, G. (1993) J. Lipid Res., 34, 1093–1106.

    PubMed  CAS  Google Scholar 

  163. Libby, P., Miao, P., Ordovas, J. M., and Schaffer, E. J. (1985) J. Cell. Physiol., 124, 1–8.

    Article  PubMed  CAS  Google Scholar 

  164. Handwerger, S., Myers, S., Richards, R., Richardson, B., Turzai, L., Moeykins, C., Meyer, T., and Anantharamahiah, G. M. (1995) Endocrinology, 136, 5555–5560.

    Article  PubMed  CAS  Google Scholar 

  165. Zhou, X., and von Eckardstein, A. (2002) J. Huazhong. Univ. Sci. Technol. Med. Sci., 22, 270–272.

    PubMed  CAS  Google Scholar 

  166. Kockx, M., Rye, K. A., Gaus, K., Quinn, C. M., Wright, J., Sloane, T., Sviridov, D., Fu, Y., Sullivan, D., Burnett, J. R., Rust, S., Assmann, G., Anantharamaiah, G. M., Palgunachari, M. N., Katz, S. L., Phillips, M. C., Dean, R. T., Jessup, W., and Kritharides, L. (2004) J. Biol. Chem., 279, 25966–25977.

    Article  PubMed  CAS  Google Scholar 

  167. Yamato, K., Tamasawa, N., Murakami, H., Matsui, J., Tanabe, J., Suda, T., and Yasujima, M. (2005) Diabetes Res. Clin. Pract., 69, 124–128.

    Article  PubMed  CAS  Google Scholar 

  168. Hyka, N., Dayer, J.-M., Modoux, C., Kohno, T., Edwards, III, C. K., Roux-Lombard, P., and Burger, D. (2001) Blood, 97, 2381–2389.

    Article  PubMed  CAS  Google Scholar 

  169. Araneo, B. A., Dowell, T., Diegel, M., and Daynes, R. A. (1991) Blood, 78, 688–699.

    PubMed  CAS  Google Scholar 

  170. Mekata, H. (1971) Nagoya J. Med. Sci., 34, 89–99.

    PubMed  CAS  Google Scholar 

  171. Panin, L. E., Kharkovski, A. V., and Usynin, I. F. (2000) Byul. Eksp. Biol. Med., 129, 171–173.

    Article  CAS  Google Scholar 

  172. Brix, K., Wirtz, R., and Herzog, V. (1997) Hepatology, 26, 1232–1240.

    PubMed  CAS  Google Scholar 

  173. Watanabe, J., Kanai, K., and Kanamura, S. (1988) J. Histochem. Cytochem., 36, 1081–1089.

    PubMed  CAS  Google Scholar 

  174. Soda, R., and Tavassoli, M. (1983) Exp. Cell Res., 145, 389–395.

    Article  PubMed  CAS  Google Scholar 

  175. Ansorge, S., Wiederanders, B., Riemann, S., Brouwer, A., and Knook, D. (1984) Biomed. Biochim. Acta, 11, 1213–1221.

    Google Scholar 

  176. Terpstra, V., and van Berkel, T. J. (2000) Blood, 95, 2157–2163.

    PubMed  CAS  Google Scholar 

  177. LeBouton, A. V. (1968) Curr. Mod. Biol., 2, 111–114.

    PubMed  CAS  Google Scholar 

  178. LeBouton, A. V. (1976) Anat. Rec., 184, 679–687.

    Article  PubMed  CAS  Google Scholar 

  179. Pyatnitskii, N. N., Zhminchenko, V. M., Sugonyaeva, N. P., Ottesyan, B. V., Kas’yanenko, V. V., and Akhmetaliev, S. G. (1977) Byul. Eksp. Biol. Med., No. 2, 214–216.

  180. Minuk, G. Y. (2003) Can. J. Gastroenterol., 17, 418–424.

    PubMed  CAS  Google Scholar 

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  1. Institute of Biochemistry, Siberian Division of the Russian Academy of Medical Sciences, ul. Akademika Timakova 2, 630117, Novosibirsk, Russia

    I. F. Usynin & L. E. Panin

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  1. I. F. Usynin
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  2. L. E. Panin
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Original Russian Text © I. F. Usynin, L. E. Panin, 2008, published in Biokhimiya, 2008, Vol. 73, No. 4, pp. 453–468.

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Usynin, I.F., Panin, L.E. Mechanisms determining phenotypic heterogeneity of hepatocytes. Biochemistry Moscow 73, 367–380 (2008). https://doi.org/10.1134/S0006297908040019

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