Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1992 Dec;83(12):1262–1266. doi: 10.1111/j.1349-7006.1992.tb02756.x

Immunohistochemical Localization of Hepatocyte Growth Factor Protein in Pancreas Islet A‐Cells of Man and Rats

Hiroyuki Tsuda 1, Teruhiko Iwase 1, Kazuyuki Matsumoto 1, Mitsuya Ito 1, Iwao Hirono 1, Yoshihisa Nishida 2, Masami Yamamoto 3, Masae Tatematsu 3, Kunio Matsumoto 4, Toshikazu Nakamura 4
PMCID: PMC5918732  PMID: 1362429

Abstract

Hepatocyte growth factor (HGF), a potent mitogen for adult rat hepatocytes in primary culture, has previously been shown to be primarily expressed in the nonparenchymal cells of the liver. Using polyclonal antisera against human and rat HGFs we studied the tissue distribution of HGF immunohistochemically and found the most intense staining in the pancreas islet cells in both man (autopsy cases) and the rat. Differential localization of 4 pancreas islet hormones, glucagon, insulin, somatostatin and pancreatic polypeptide, revealed HGF to be preferentially expressed within the glucagon‐positive cells. The results indicate that HGF is primarily produced or stored in A‐cells and may act as a growth factor in a paracrine and an endocrine fashion, like various other hormones.

Keywords: Hepatocyte growth factor, Pancreas islet A‐cell, Immunohistochemistry

Full Text

The Full Text of this article is available as a PDF (502.5 KB).

REFERENCES

  • 1. ) Nakamura , T. , Teramoto , H. and Ichihara , A.Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures . Proc. Natl. Acad. Sci. USA , 83 , 6489 – 6493 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. ) Nakamura , T. , Nawa , K. , Ichihara , N. and Nishino , T.Purification and subunit structure of hepatocyte growth factor from rat platelets . FEBS Lett. , 224 , 311 – 316 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Nakamura , T. , Nawa , K. and Ichihara , A.Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats . Biochem. Biophys. Res. Commun. , 122 , 1450 – 1459 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Zarnegar , R. , DeFrances , M. C. , Kost , D. P. , Lindroos , P. and Michalopoulos , G. K.Expression of hepatocyte growth factor mRNA in regenerating rat liver after partial hepatectomy . Biochem. Biophys. Res. Commun. , 177 , 559 – 565 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Higuchi , O. and Nakamura , T.Identification and change in the receptor hepatocyte growth factor in rat liver after partial hepatectomy or induced hepatitis . Biochem. Biophys. Res. Commun. , 176 , 599 – 607 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Igawa , T. , Kanda , S. , Kanetake , H. , Saitoh , Y. , Ichihara , A. , Tomita , Y. and Nakamura , T.Hepatocyte growth factor is a potent mitogen for cultured rabbit renal tubular epithelial cells . Biochem. Biophys. Res. Commun. , 174 , 831 – 838 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Gohda , E. , Tsubouchi , H. , Nakayama , H. , Hirono , S. , Arakaki , N. , Yamamoto , I. , Hashimoto , S. and Daikuhara , Y.Human hepatocyte growth factor in blood of patients with fulminant hepatic failure. Basic aspects . Dig. Dis. Sci. , 36 , 785 – 790 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Shimizu , I. , Ichihara , A. and Nakamura , T.Hepatocyte growth factor in ascites from patients with cirrhosis . J. Biochem. , 109 , 14 – 18 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Lindroos , P. M. , Zarnegar , R. and Michalopoulos , G. K.Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DNA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetra‐chloride administration . Hepatology , 13 , 743 – 750 ( 1991. ). [PubMed] [Google Scholar]
  • 10. ) Nakamura , T.Structure and function of hepatocyte growth factor . Prog. Growth Factor Res. , 3 , 67 – 85 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Matsumoto , K. and Nakamura , T.Hepatocyte growth factor: molecular structure, roles in liver regeneration, and other biological functions . Crit. Rev. Oncogenesis , 3 , 27 – 54 ( 1992. ). [PubMed] [Google Scholar]
  • 12. ) Nakamura , T. , Nishizawa , T. , Hagiya , M. , Seki , T. , Shimonishi , M. and Shimizu , S.Molecular cloning and experssion of human hepatocyte growth factor . Nature , 342 , 440 – 443 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Miyazawa , K. , Tsubouchi , H. , Naka , D. , Takahashi , K. , Okigaki , M. , Gohda , E. , Daikuhara , N. and Kitamura , N.Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor . Biochem. Biophys. Res. Commun. , 163 , 967 – 973 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Tashiro , K. , Hagiya , M. , Nishizawa , T. , Seki , T. , Shimonishi , M. , Shimizu , S. and Nakamura , T.Deduced primary structure of rat hepatocyte growth factor and expression of the mRNA in rat tissues . Proc. Natl. Acad. Sci. USA , 87 , 3200 – 3204 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. ) Noji , S. , Tashiro , K. , Koyama , E. , Nohno , T. , Ohyama , K. , Taniguchi , S. and Nakamura , T.Expression of hepatocyte growth factor gene in endothelial and Kupffer cells of damaged rat livers, as revealed by in situ hybridization . Biochem. Biophys. Res. Commun. , 173 , 42 – 47 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Bottaro , D. P. , Rubin , J. S. , Faletto , D. L. , Chan , A. M. , Kmiecik , T. E. , Vande , W. G. and Aaronson , S. A.Identification of the hepatocyte growth factor receptor as the c‐met proto‐oncogene product . Science , 251 , 802 – 804 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Di Renzo , M. , Narsimhan , R. P. , Olivero , M. , Bretti , S. , Giordano , S. , Medico , E. , Gaglia , P. , Zara , P. and Comoglio , P. M.Expression of the Met/HGF receptor in normal and neoplastic human tissues . Oncogene , 6 , 1997 – 2003 ( 1991. ). [PubMed] [Google Scholar]
  • 18. ) Zarnegar , R. , Muga , S. , Rahija , R. and Michalopoulos , G.Tissue distribution of hepatopoietin‐A: a heparin‐binding polypeptide growth factor for hepatocytes . Proc. Natl. Acad. Sci. USA , 87 , 1252 – 1256 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Wolf , H. K. , Zarnegar , R. , Oliver , L. and Michalopoulos , G. K.Hepatocyte growth factor in human placenta and trophoblastic disease . Am. J. Pathol , 138 , 1035 – 1043 ( 1991. ). [PMC free article] [PubMed] [Google Scholar]
  • 20. ) Kan , M. , Zhang , G. H. , Zarnegar , R. , Michalopoulos , G. , Myoken , Y. , McKeehan , W. L. and Stevens , J. I.Hepatocyte growth factor/hepatopoietin A stimulates the growth of rat kidney proximal tubule epithelial cells (RPTE), rat nonparenchymal liver cells, human melanoma cells, mouse keratinocytes and stimulates anchorage‐independent growth of SV‐40 transformed RPTE . Biochem, Biophys. Res. Commun. , 174 , 331 – 337 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Matsumoto , K. , Hashimoto , K. , Yoshikawa , K. and Nakamura , T.Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor . Exp. Cell. Res. , 196 , 114 – 120 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Matsumoto , K. , Tajima , H. and Nakamura , T.Hepatocyte growth factor is a potent stimulator of human melanocyte DNA synthesis and growth . Biochem. Biophys. Res. Commun. , 176 , 45 – 51 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Rubin , J. S. , Chan , A. M. , Bottaro , D. P. , Burgess , W. H. , Taylor , W. G. , Cech , A. C. , Hirschfield , D. W. , Wong , J. , Miki , T. , Finch , P. W. and Aaronson , S. A.A broad‐spectrum human lung fibroblast‐derived mitogen is a variant of hepatocyte growth factor . Proc. Natl. Acad. Sci. USA , 88 , 415 – 419 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. ) Nagaike , M. , Hirao , S. , Tajima , H. , Noji , S. , Taniguchi , S. , Matsumoto , K. and Nakamura , T.Renotropic functions of hepatocyte growth factor in renal regeneration after unilateral nephrectomy . J. Biol. Chem. , 266 , 22781 – 22784 ( 1991. ). [PubMed] [Google Scholar]
  • 25. ) Seki , T. , Ihara , L. , Sugimura , A. , Shimonishi , M. , Nishizawa , T. , Asami , O. , Hagiya , M. , Nakamura , T. and Shimizu , S.Isolation and expression of cDNA for the human hepatocyte growth factor from human leucocytes . Biochem. Biophys. Res. Commun. , 172 , 321 – 327 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Montesano , R. , Matsumoto , K. , Nakamura , T. and Orci , L.Identification of a fibroblast‐derived epithelial morpho‐gen as hepatocyte growth factor . Cell , 67 , 901 – 908 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Hsu , S. M. , Raine , L. and Farger , H.Use of avidin‐biotin‐peroxidase complex (ABC) in immunohistochemical techniques: a comparison between ABC and unlabelled antibody PAP procedures . J. Histochem. Cytochem. , 29 , 577 – 580 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 28. ) Nanbe , K. , Aoki , J. and Sasaki , N.A new enzyme immunohistochemical technique using alkaline phospha‐tase‐labelled avidin and new fuchsin . Byori to Rinshou (Pathol. Clin. Med. ), 5 , 333 – 339 ( 1987. ) ( in Japanese ). [Google Scholar]
  • 29. ) Mason , D. Y. and Sammons , R.Alkaline phosphatase and peroxidase for double immunoenzymatic labelling of cellular constituents . J. Clin. Pathol , 31 , 454 – 460 ( 1978. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. ) Wolf , H. K. , Zarnegar , R. and Michalopoulos , G. K.Localization of hepatocyte growth factor in human and rat tissues: an immunohistochemical study . Hepatology , 14 , 488 – 494 ( 1991. ). [PubMed] [Google Scholar]
  • 31. ) Yanagita , K. , Nagaike , M. , Ishibashi , H. , Niho , Y. , Matsumoto , K. and Nakamura , T.Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs . Biochem. Biophys. Res. Commun. , 182 , 802 – 809 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 32. ) Ishibashi , K. , Sasaki , S. , Sakamoto , H. , Nakamura , Y. , Hara , T. , Nakamura , T. and Marumo , F.Hepatocyte growth factor is a paracrine factor for renal epithelial cells: stimulation of DNA synthesis and NA, K‐ATPase activity . Biochem. Biophys. Res. Commun. , 182 , 960 – 965 ( 1992. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES