Tissue distribution of hepatopoietin-A: a heparin-binding polypeptide growth factor for hepatocytes (original) (raw)

Abstract

Hepatopoietin-A (HPTA) is a heparin-binding polypeptide growth factor which consists of a heavy and a light polypeptide chain with molecular weights of 70,000 and 35,000, respectively. It stimulates DNA synthesis in primary cultures of normal rat hepatocytes in serum-free medium. The complete purification and characterization of HPTA from rabbit serum were reported by us elsewhere. Recently we have determined the amino-terminal amino acid sequence of the rabbit HPTA light chain up to 24 residues and have shown that the sequence is not homologous with other known sequences. [N.B. Human hepatocyte growth factor, recently sequenced by two other groups, is the same molecular species as HPTA.] In the present paper we report the production of a neutralizing polyclonal antiserum raised in chicken against purified rabbit HPTA. This antiserum does not inhibit the mitogenic effect of other potent inducers of hepatocyte DNA synthesis (epidermal growth factor or acidic fibroblast growth factor), nor does it interact with these growth factors in an enzyme-linked immunosorbent assay (ELISA). The antibody recognizes HPTA, as was determined by Western immunoblotting. Since the tissue origin of HPTA is not known, this anti-HPTA antiserum was used to investigate the tissue distribution of HPTA in rabbits by immunohistostaining methods. Acinar cells of the pancreas, neurons of the brain, C cells of the thyroid, ductal cells of the salivary glands, and Brunners glands of the duodenum stained with anti-HPTA antibody. Liver, spleen, thymus, and kidney do not seem to contain appreciable amounts of HPTA. We confirmed these findings by extracting and purifying active HPTA from the stained tissues listed above. The anti-HPTA antibody recognizes HPTA purified from different tissues, as was determined by ELISA, Western immunoblotting, and immunoneutralization experiments.

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  1. Braun L., Mead J. E., Panzica M., Mikumo R., Bell G. I., Fausto N. Transforming growth factor beta mRNA increases during liver regeneration: a possible paracrine mechanism of growth regulation. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1539–1543. doi: 10.1073/pnas.85.5.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Coffey R. J., Jr, Kost L. J., Lyons R. M., Moses H. L., LaRusso N. F. Hepatic processing of transforming growth factor beta in the rat. Uptake, metabolism, and biliary excretion. J Clin Invest. 1987 Sep;80(3):750–757. doi: 10.1172/JCI113130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cruise J. L., Knechtle S. J., Bollinger R. R., Kuhn C., Michalopoulos G. Alpha 1-adrenergic effects and liver regeneration. Hepatology. 1987 Nov-Dec;7(6):1189–1194. doi: 10.1002/hep.1840070604. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Fisher B., Szuch P., Levine M., Fisher E. R. A portal blood factor as the humoral agent in liver regeneration. Science. 1971 Feb 12;171(3971):575–577. doi: 10.1126/science.171.3971.575. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. GRISHAM J. W., LEONG G. F., HOLE B. V. HETEROTOPIC PARTIAL AUTOTRANSPLANTATION OF RAT LIVER: TECHNIC AND DEMONSTRATION OF STRUCTURE AND FUNCTION OF THE GRAFT. Cancer Res. 1964 Sep;24:1474–1495. [PubMed] [Google Scholar]
  8. Gohda E., Tsubouchi H., Nakayama H., Hirono S., Sakiyama O., Takahashi K., Miyazaki H., Hashimoto S., Daikuhara Y. Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure. J Clin Invest. 1988 Feb;81(2):414–419. doi: 10.1172/JCI113334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gohda E., Tsubouchi H., Nakayama H., Hirono S., Takahashi K., Koura M., Hashimoto S., Daikuhara Y. Human hepatocyte growth factor in plasma from patients with fulminant hepatic failure. Exp Cell Res. 1986 Sep;166(1):139–150. doi: 10.1016/0014-4827(86)90514-8. [DOI] [PubMed] [Google Scholar]
  10. Goldberg M. Purification and partial characterization of a liver cell proliferation factor called hepatopoietin. J Cell Biochem. 1985;27(3):291–302. doi: 10.1002/jcb.240270310. [DOI] [PubMed] [Google Scholar]
  11. Houck K. A., Cruise J. L., Michalopoulos G. Norepinephrine modulates the growth-inhibitory effect of transforming growth factor-beta in primary rat hepatocyte cultures. J Cell Physiol. 1988 Jun;135(3):551–555. doi: 10.1002/jcp.1041350327. [DOI] [PubMed] [Google Scholar]
  12. Jirtle R. L., Michalopoulos G. Effects of partial hepatectomy on transplanted hepatocytes. Cancer Res. 1982 Aug;42(8):3000–3004. [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Miyazawa K., Tsubouchi H., Naka D., Takahashi K., Okigaki M., Arakaki N., Nakayama H., Hirono S., Sakiyama O., Takahashi K. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem Biophys Res Commun. 1989 Sep 15;163(2):967–973. doi: 10.1016/0006-291x(89)92316-4. [DOI] [PubMed] [Google Scholar]
  16. Moolten F. L., Bucher N. L. Regeneration of rat liver: transfer of humoral agent by cross circulation. Science. 1967 Oct 13;158(3798):272–274. doi: 10.1126/science.158.3798.272. [DOI] [PubMed] [Google Scholar]
  17. Moore G. A., McConkey D. J., Kass G. E., O'Brien P. J., Orrenius S. 2,5-Di(tert-butyl)-1,4-benzohydroquinone--a novel inhibitor of liver microsomal Ca2+ sequestration. FEBS Lett. 1987 Nov 30;224(2):331–336. doi: 10.1016/0014-5793(87)80479-9. [DOI] [PubMed] [Google Scholar]
  18. Nakamura T., Nawa K., Ichihara A. Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1450–1459. doi: 10.1016/0006-291x(84)91253-1. [DOI] [PubMed] [Google Scholar]
  19. Nakamura T., Nishizawa T., Hagiya M., Seki T., Shimonishi M., Sugimura A., Tashiro K., Shimizu S. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440–443. doi: 10.1038/342440a0. [DOI] [PubMed] [Google Scholar]
  20. Paloheimo M., Linkola J., Lempinen M., Folke M. Time-courses of hepatocellular hyperpolarization and cyclic adenosine 3',5'-monophosphate accumulation after partial hepatectomy in the rat. Effects of fasting for 48 hours and intravenous injection of glucose. Gastroenterology. 1984 Sep;87(3):639–646. [PubMed] [Google Scholar]
  21. Pettmann B., Labourdette G., Weibel M., Sensenbrenner M. The brain fibroblast growth factor (FGF) is localized in neurons. Neurosci Lett. 1986 Jul 24;68(2):175–180. doi: 10.1016/0304-3940(86)90137-0. [DOI] [PubMed] [Google Scholar]
  22. Rao M. S., Subbarao V. DNA synthesis in exocrine and endocrine pancreas after partial hepatectomy in Syrian golden hamsters. Experientia. 1986 Jul 15;42(7):833–834. doi: 10.1007/BF01941543. [DOI] [PubMed] [Google Scholar]
  23. Russell W. E., Coffey R. J., Jr, Ouellette A. J., Moses H. L. Type beta transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5126–5130. doi: 10.1073/pnas.85.14.5126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Russell W. E., McGowan J. A., Bucher N. L. Partial characterization of a hepatocyte growth factor from rat platelets. J Cell Physiol. 1984 May;119(2):183–192. doi: 10.1002/jcp.1041190207. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Smith G. L., Lyons R. M., Harkins R. N., Knauer D. J. Purification of multiplication-stimulating activity carrier protein. Methods Enzymol. 1987;146:270–277. doi: 10.1016/s0076-6879(87)46029-1. [DOI] [PubMed] [Google Scholar]
  27. Tsutsumi O., Kurachi H., Oka T. A physiological role of epidermal growth factor in male reproductive function. Science. 1986 Aug 29;233(4767):975–977. doi: 10.1126/science.3090686. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Zarnegar R., Muga S., Enghild J., Michalopoulos G. NH2-terminal amino acid sequence of rabbit hepatopoietin A, a heparin-binding polypeptide growth factor for hepatocytes. Biochem Biophys Res Commun. 1989 Sep 29;163(3):1370–1376. doi: 10.1016/0006-291x(89)91130-3. [DOI] [PubMed] [Google Scholar]
  30. de Hemptinne B., Lorge F., Kestens P. J., Lambotte L. Facteurs d'hyperpolarisation hépatocellulaire et régénération après hépatectomie partielle chez le rat. Acta Gastroenterol Belg. 1985 Jul-Aug;48(4):424–431. [PubMed] [Google Scholar]