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. 1992 Jun;33(6):831–835. doi: 10.1136/gut.33.6.831

Effect of in vivo administration of an antibody to epidermal growth factor on the rapid increase in DNA synthesis induced by partial hepatectomy in the rat.

D A Vesey 1, A C Selden 1, A C Woodman 1, H J Hodgson 1
PMCID: PMC1379345  PMID: 1624168

Abstract

Recent reports indicate that transforming growth factor alpha (TGF-alpha) is produced within the liver and acts as the natural ligand of the epidermal growth factor (EGF) receptor causing the EGF receptor down regulation and the hepatocyte proliferation observed after partial hepatectomy. The reported phenomenon that an antibody to EGF inhibits the regenerative response to partial hepatectomy was therefore re-investigated. The IgG fraction of an anti-rat EGF antibody was injected intravenously at the time of partial hepatectomy, and its effects on regenerative DNA synthesis were compared with those of non-immune IgG. Injection of IgG reduced the DNA synthetic response to partial hepatectomy, assessed 24 hours after resection by 3H-thymidine incorporation, but the effects of normal and anti-EGF IgG were not statistically different, despite the presence of excess anti-EGF IgG in the circulation throughout the experimental period. However, anti-EGF IgG could completely block the proliferative response of hepatocytes in culture to EGF. These results support the suggestion that EGF is not the major mediator of hepatocyte DNA synthesis in the early stages of liver regeneration (less than 24 hours).

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Selected References

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  1. Alison M. R. Regulation of hepatic growth. Physiol Rev. 1986 Jul;66(3):499–541. doi: 10.1152/physrev.1986.66.3.499. [DOI] [PubMed] [Google Scholar]
  2. Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969 Dec;43(3):506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Earp H. S., O'Keefe E. J. Epidermal growth factor receptor number decreases during rat liver regeneration. J Clin Invest. 1981 May;67(5):1580–1583. doi: 10.1172/JCI110190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fabrikant J. I. Kinetic analysis of hepatic regeneration. Growth. 1967 Dec;31(4):311–315. [PubMed] [Google Scholar]
  5. GRISHAM J. W. A morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating rat liver; autoradiography with thymidine-H3. Cancer Res. 1962 Aug;22:842–849. [PubMed] [Google Scholar]
  6. Gruppuso P. A., Mead J. E., Fausto N. Transforming growth factor receptors in liver regeneration following partial hepatectomy in the rat. Cancer Res. 1990 Mar 1;50(5):1464–1469. [PubMed] [Google Scholar]
  7. Kan M., Huang J. S., Mansson P. E., Yasumitsu H., Carr B., McKeehan W. L. Heparin-binding growth factor type 1 (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7432–7436. doi: 10.1073/pnas.86.19.7432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. LaBrecque D. R., Steele G., Fogerty S., Wilson M., Barton J. Purification and physical-chemical characterization of hepatic stimulator substance. Hepatology. 1987 Jan-Feb;7(1):100–106. doi: 10.1002/hep.1840070121. [DOI] [PubMed] [Google Scholar]
  9. Marti U., Burwen S. J., Jones A. L. Biological effects of epidermal growth factor, with emphasis on the gastrointestinal tract and liver: an update. Hepatology. 1989 Jan;9(1):126–138. doi: 10.1002/hep.1840090122. [DOI] [PubMed] [Google Scholar]
  10. McGowan J. A., Strain A. J., Bucher N. L. DNA synthesis in primary cultures of adult rat hepatocytes in a defined medium: effects of epidermal growth factor, insulin, glucagon, and cyclic-AMP. J Cell Physiol. 1981 Sep;108(3):353–363. doi: 10.1002/jcp.1041080309. [DOI] [PubMed] [Google Scholar]
  11. Mead J. E., Fausto N. Transforming growth factor alpha may be a physiological regulator of liver regeneration by means of an autocrine mechanism. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1558–1562. doi: 10.1073/pnas.86.5.1558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Michalopoulos G. K. Liver regeneration: molecular mechanisms of growth control. FASEB J. 1990 Feb 1;4(2):176–187. [PubMed] [Google Scholar]
  13. Michalopoulos G., Houck K. A., Dolan M. L., Leutteke N. C. Control of hepatocyte replication by two serum factors. Cancer Res. 1984 Oct;44(10):4414–4419. [PubMed] [Google Scholar]
  14. Moore J. B., Jr Purification and partial characterization of epidermal growth factor isolated from the male rat submaxillary gland. Arch Biochem Biophys. 1978 Jul;189(1):1–7. doi: 10.1016/0003-9861(78)90106-6. [DOI] [PubMed] [Google Scholar]
  15. Munro H. N. The determination of nucleic acids. Methods Biochem Anal. 1966;14:113–176. doi: 10.1002/9780470110324.ch5. [DOI] [PubMed] [Google Scholar]
  16. Nakamura T., Nawa K., Ichihara A., Kaise N., Nishino T. Purification and subunit structure of hepatocyte growth factor from rat platelets. FEBS Lett. 1987 Nov 30;224(2):311–316. doi: 10.1016/0014-5793(87)80475-1. [DOI] [PubMed] [Google Scholar]
  17. Rall L. B., Scott J., Bell G. I., Crawford R. J., Penschow J. D., Niall H. D., Coghlan J. P. Mouse prepro-epidermal growth factor synthesis by the kidney and other tissues. Nature. 1985 Jan 17;313(5999):228–231. doi: 10.1038/313228a0. [DOI] [PubMed] [Google Scholar]
  18. Raper S. E., Burwen S. J., Barker M. E., Jones A. L. Translocation of epidermal growth factor to the hepatocyte nucleus during rat liver regeneration. Gastroenterology. 1987 May;92(5 Pt 1):1243–1250. doi: 10.1016/s0016-5085(87)91084-5. [DOI] [PubMed] [Google Scholar]
  19. Schacterle G. R., Pollack R. L. A simplified method for the quantitative assay of small amounts of protein in biologic material. Anal Biochem. 1973 Feb;51(2):654–655. doi: 10.1016/0003-2697(73)90523-x. [DOI] [PubMed] [Google Scholar]
  20. Selden C., Hodgson H. J. Further characterisation of 'hepatotropin', a high molecular weight hepatotrophic factor in rat serum. J Hepatol. 1989 Sep;9(2):167–176. doi: 10.1016/0168-8278(89)90047-0. [DOI] [PubMed] [Google Scholar]
  21. Selden C., Johnstone R., Darby H., Gupta S., Hodgson H. J. Human serum does contain a high molecular weight hepatocyte growth factor: studies pre- and post-hepatic resection. Biochem Biophys Res Commun. 1986 Aug 29;139(1):361–366. doi: 10.1016/s0006-291x(86)80122-x. [DOI] [PubMed] [Google Scholar]
  22. Selden C., Jones M., Wade D., Hodgson H. Hepatotropin mRNA expression in human foetal liver development and in liver regeneration. FEBS Lett. 1990 Sep 17;270(1-2):81–84. doi: 10.1016/0014-5793(90)81239-k. [DOI] [PubMed] [Google Scholar]
  23. Skov Olsen P., Boesby S., Kirkegaard P., Therkelsen K., Almdal T., Poulsen S. S., Nexø E. Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats. Hepatology. 1988 Sep-Oct;8(5):992–996. doi: 10.1002/hep.1840080503. [DOI] [PubMed] [Google Scholar]
  24. St Hilaire R. J., Hradek G. T., Jones A. L. Hepatic sequestration and biliary secretion of epidermal growth factor: evidence for a high-capacity uptake system. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3797–3801. doi: 10.1073/pnas.80.12.3797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stirling G. A., Bourne L. D., Marsh T. Effect of protein deprivation and a reduced diet on the regenerating rat liver. Br J Exp Pathol. 1975 Dec;56(6):502–509. [PMC free article] [PubMed] [Google Scholar]
  26. Talarico K. S., Feller D. D., Neville E. D. Mitotic response to various dietary conditions in the normal and regenerating rat liver. Proc Soc Exp Biol Med. 1971 Feb;136(2):381–384. doi: 10.3181/00379727-136-35269. [DOI] [PubMed] [Google Scholar]
  27. Ullrich A., Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990 Apr 20;61(2):203–212. doi: 10.1016/0092-8674(90)90801-k. [DOI] [PubMed] [Google Scholar]
  28. Wollenberg G. K., Harris L., Farber E., Hayes M. A. Inverse relationship between epidermal growth factor induced proliferation and expression of high affinity surface epidermal growth factor receptors in rat hepatocytes. Lab Invest. 1989 Feb;60(2):254–259. [PubMed] [Google Scholar]
  29. Zarnegar R., Michalopoulos G. Purification and biological characterization of human hepatopoietin A, a polypeptide growth factor for hepatocytes. Cancer Res. 1989 Jun 15;49(12):3314–3320. [PubMed] [Google Scholar]

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