Digestive Diseases and Sciences

, Volume 40, Issue 5, pp 1132–1139 | Cite as

Roles of hepatocyte growth factor and its receptor in gastric mucosa

A cell biological and molecular biological study
  • Shingo Tsuji
  • Sunao Kawano
  • Masahiko Tsujii
  • Hideyuki Fusamoto
  • Takenobu Kamada
Esophageal, Gastric, And Duodenal Disorders


Hepatocyte growth factor (HGF) stimulates the growth of hepatocytes and other epithelial cells. A gene for the HGF receptor,c-met, is detected in the intestinal tract and the liver, as well as in gastric carcinoma cells. However, the role of HGF in the regeneration of the normal gastric mucosa is not known. The purpose of the present study was to elucidate the effects of HGF on the morphogenesis of cultured gastric mucosal cells and to evaluate the role of HGF andc-met in the healing process in rat gastric mucosa. The cultured gastric mucosal cells developed a branching morphology in a collagen matrix supplemented with HGF or fetal calf serum. They did not form this morphology on a plastic dish or in the collagen without HGF or the serum. In anin vivo study, total RNA was extracted from rat gastric mucosa 6, 24, 48, and 96 hr after the exposure to a solution of 0.6 M HCl. HGF messenger RNA was not detected, butc-met was expressed in the mucosa. The increased expression ofc-met was followed by healing of the mucosal injury. These results indicate that HGF plays important roles in the morphogenesis of gastric mucosal cells and that the HGF receptor gene participates in the healing process of gastric mucosa.

Key words

hepatocyte growth factor c-met rat stomach morphogenesis 


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  1. 1.
    Tashiro K, Hagiya M, Nishizawa T, Seki T, Shimonishi M, Shimizu S, 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, 1990PubMedGoogle Scholar
  2. 2.
    Nakamura T: Structure and function of hepatocyte growth factor. Prog Growth Factor Res 3:67–85, 1991PubMedGoogle Scholar
  3. 3.
    Wolf HK, Zarnegar R, Michalopoulos GK: Localization of hepatocyte growth factor in human and rat tissues: An immunohistochemical study. Hepatology 14:488–494, 1991PubMedGoogle Scholar
  4. 4.
    Fausto N: Growth factors in liver development, regeneration and carcinogenesis. Prog Growth Factor Res 3:219–234, 1991PubMedGoogle Scholar
  5. 5.
    Matsumoto K, Nakamura T: Hepatocyte growth factor: Molecular structure, roles in liver regeneration, and other biological functions. Crit Rev Oncog 3:27–54, 1992PubMedGoogle Scholar
  6. 6.
    Takahashi M, Ota S, Terano A, Yoshimura K, Matsumura M, Niwa Y PM, Kawabe T, Nakamura T, Omata M: Hepatocyte growth factor induces mitogenic reaction to the rabbit gastric epithelial cells in primary culture. Biochem Biophys Res Commun 191:528–534, 1993PubMedGoogle Scholar
  7. 7.
    Dean M, Park M, Le Beau MM, Robins TS, Diaz MO, Rowley JD, Blair DG, Vande Woude GF: The humanmet oncogene is related to the tyrosine kinase oncogenes. Nature 318:385–388, 1985PubMedGoogle Scholar
  8. 8.
    Bottaro DP, Rubin JS, Faletto DL, Chan AM-L, Kmiecik TE, VandeWoude GF, Aaronson SA: Identification of the hepatocyte growth factor receptor as thec-met proto-oncogene product. Science 251:802–804, 1991PubMedGoogle Scholar
  9. 9.
    Strain AJ, Ismail T, Tsubouchi H, Arakaki N, Hishida T, Kitamura N, Daikuhara Y, McMaster P: Native and recombinant human hepatocyte growth factors are highly potent promoters of DNA synthesis in both human and rat hepatocytes. J Clin Invest 87:1853–1857, 1991PubMedGoogle Scholar
  10. 10.
    Lindroos PM, Zarnegar R, Michalopoulas GK: Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DNA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetrachloride administration. Hepatology 13:743–749, 1991PubMedGoogle Scholar
  11. 11.
    Tsujii M, Kawano S, Tsuji S, Ito T, Hayashi N, Horimoto M, Mita E, Nagano K, Masuda E, Hayashi N, Fusamoto H, Kamada T: Increased expression ofc-met messenger RNA following acute gastric injury in rats. Biochem Biophys Res Commun 200:536–541, 1994PubMedGoogle Scholar
  12. 12.
    Chan AM-L, King HWS, Deakin EA, Tempest PR, Hilkens J, Kroezen V, Edwards DR, Wills AJ, Brookes P, Cooper CS: Characterization of the mousemet proto-oncogene. Oncogene 2:593–599, 1988PubMedGoogle Scholar
  13. 13.
    Yang J, Nandi S: Growth of cultured cells using collagen substrate. Int Rev Cytol 81:249–286, 1983PubMedGoogle Scholar
  14. 14.
    Yang J, Richards J, Bowman P, Guzmar R, Enami J, McCormick K, Hamamoto S, Pitelka DR, Nandi S: Sustained growth and three-dimensional organization of primary mammary tumor epithelial cells embedded in collagen gel. Proc Natl Acad Sci USA 76:3401–3405, 1979PubMedGoogle Scholar
  15. 15.
    Haeuptle MT, Suard YLM, Bogenmann GR, Reggio H, Racine L, Kraehenbuhl JP: Effect of cell shape change on the function and differentialtion of rabbit mammary cells in culture. J Cell Biol 96:1425–1434, 1983PubMedGoogle Scholar
  16. 16.
    Tsubouchi H, Niitani Y, Hirono S, Nakayama H, Gohda E, Arakaki N, Sakiyama N, Takahashi K, Kimoto M, Kawakami S, Setoguchi M, Tachikawa T, Shin S, Arima T, Daikuhara Y: Levels of the human hepatocyte growth factor in serum of patients with various liver diseases determined by an enzyme-linked immunosorbent assay. Hepatology 13:1–5, 1991PubMedGoogle Scholar
  17. 17.
    Seki T, Ihara I, Sugimura A, Shimonishi M, Nishizawa T, Asami O, Hagiya M, Nakamura T, Shimizu S: Isolation and expression of cDNA for different forms of hepatocyte growth factor from human leukocyte. Biochem Biophys Res Commun 172:321–327, 1990PubMedGoogle Scholar
  18. 18.
    Di Renzo MF, Narsimhan RP, Olivero M, Bretti S, Giordano S, Medico E, Gaglia P, Zara P, Comoglio PM: Expression of theMet/HGF receptor in normal and neoplastic human tissues. Oncogene 6:1997–2003, 1991PubMedGoogle Scholar
  19. 19.
    Prat M, Narsimhan RP, Crepaldi T, Nocotra MR, Natali PG, Comoglio PM: The receptor encoded by the human c-met oncogene is expressed in hepatocytes, epithelial cells and solid tumors. Int J Cancer 49:323–328, 1991PubMedGoogle Scholar
  20. 20.
    Ponzetto C, Giordano S, Peverali F, Della Valle G, Abate ML, Vaula G, Comoglio PM:c-met is amplified but not mutated in a cell line with an activated met tyrosine kinase. Oncogene 6:553–559, 1991PubMedGoogle Scholar
  21. 21.
    Shibamoto S, Hayakawa M, Hori T, Oku N, Miyazawa K, Kitamura N, Ito F: Hepatocyte growth factor and transforming growth factor beta stimulate both cell growth and migration of human gastric adenocarcinoma cells. Cell Struct Funct 17:185–190, 1992PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Shingo Tsuji
    • 1
  • Sunao Kawano
    • 1
  • Masahiko Tsujii
    • 1
  • Hideyuki Fusamoto
    • 1
  • Takenobu Kamada
    • 1
  1. 1.First Department of MedicineOsaka UniversitySuitaJapan

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