Skip to main content

Advertisement

SpringerLink
Log in

High Expression of Gastrin Receptor Protein in Injured Mucosa of Helicobacter pylori-Positive Gastritis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background and Aim

Gastrin is a growth factor for the gastric epithelial cells. However, it is unknown how gastric receptor (GR) expression is regulated in the gastric mucosa. We studied GR expression using a newly raised antibody and investigated the relationship between GR expression and gastritis.

Methods

Gastric receptor expression in 63 human gastric mucosa was studied. Helicobacter pylori infection and histological gastritis status were evaluated in gastric biopsy samples. In gastric ulcer cases, additional biopsy specimens were taken from injured mucosa. Fasting sera were collected and serum gastrin level evaluated. MKN-28 cells were cultured at various pH conditions, and the change in GR expression was determined.

Results

Gastric receptor expression was detected in the foveolar epithelium of the gastric mucosa, and its expression was stronger in patients infected with H. pylori. In particular, higher expression was detected in regenerating injured mucosa. There was no association between gastritis score/serum gastrin level and GR expression in H. pylori-positive cases. In MKN-28 cells, GR protein expression was lower in neutral conditions than in acidic or alkaline conditions.

Conclusion

Gastric mucosal injury with H. pylori infection destroys the pH barrier on the foveolar epithelium and may induce GR expression through pH changes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

GR:

Gastrin receptor

PPI:

Proton pump inhibitor

H. pylori :

Helicobacter pylori

References

  1. Tahara E. Growth factors and oncogenes in human gastrointestinal carcinomas. J Cancer Res Clin Oncol. 1990;116:121–131.

    Article  PubMed  CAS  Google Scholar 

  2. Ochiai A, Yasui W, Tahara E. Growth-promoting effect of gastrin on human gastric carcinoma cell line TMK-1. Jpn J Cancer Res. 1985;76:1064–1071.

    PubMed  CAS  Google Scholar 

  3. Naito Y, Ito M, Watanabe T, Suzuki H. Biomarkers in patients with gastric inflammation: a systematic review. Digestion. 2005;72:164–180.

    Article  PubMed  Google Scholar 

  4. Ito M, Haruma K, Kaya S, et al. Serological comparison of serum pepsinogen and anti-parietal cell antibody levels between Japanese and German patients. Eur J Gastroenterol Hepatol. 2002;14:123–127.

    Article  PubMed  CAS  Google Scholar 

  5. Watson SA, Grabowska AM, El-Zaatari M, Takhar A. Gastrin-active participant or bystander in gastric carcinogenesis? Nat Rev Cancer. 2006;12:936–946.

    Article  Google Scholar 

  6. Ose T, Kadowaki Y, Fukuhara H, et al. Reg I-knockout mice reveal its role in regulation of cell growth that is required in generation and maintenance of the villous structure of small intestine. Oncogene. 2007;26:349–359.

    Article  PubMed  CAS  Google Scholar 

  7. Chiba T, Fukui H, Kinoshita Y. Reg protein: a possible mediator of gastrin-induced mucosal cell growth. J Gastroenterol. 2000;35:52–56.

    Article  PubMed  CAS  Google Scholar 

  8. Sumiyoshi H, Yasui W, Ochiai A, Tahara E. Effects of gastrin on tumor growth and cyclic nucleotide metabolism in xenotransplantable human gastric and colonic carcinomas in nude mice. Cancer Res. 1984;44:4276–4280.

    PubMed  CAS  Google Scholar 

  9. McWilliams DF, Watson SA, Crosbee DM, Michaeli D, Seth R. Coexpression of gastrin and gastrin receptors (CCK-B and delta CCK-B) in gastrointestinal tumour cell lines. Gut. 1998;42:795–798.

    Article  PubMed  CAS  Google Scholar 

  10. Lee YM, Beinborn M, McBride EW, Lu M, Kolakowski LF Jr, Kopin AS. The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization. J Biol Chem. 1993;268:8164–8169.

    PubMed  CAS  Google Scholar 

  11. Kazumori H, Ishihara S, Kawashima K, Fukuda R, Chiba T, Kinoshita Y. Analysis of gastrin receptor gene expression in proliferating cells in the neck zone of gastric fundic glands using laser capture microdissection. FEBS Lett. 2001;489:208–214.

    Article  PubMed  CAS  Google Scholar 

  12. Schmitz F, Göke MN, Otte JM, et al. Cellular expression of CCK-A and CCK-B/gastrin receptors in human gastric mucosa. Regul Pept. 2001;102:101–110.

    Article  PubMed  CAS  Google Scholar 

  13. Kulaksiz H, Arnold R, Goke B, et al. Expression and cell-specific localization of the cholecystokinin B/gastrin receptor in the human stomach. Cell Tissue Res. 2000;299:289–298.

    Article  PubMed  CAS  Google Scholar 

  14. Henwood M, Clarke PA, Smith AM, Watson SA. Expression of gastrin in developing gastric adenocarcinoma. Br J Surg. 2001;88:564–568.

    Article  PubMed  CAS  Google Scholar 

  15. Kumamoto T, Sumii K, Haruma K, Tari A, Tanaka K, Kajiyama G. Gastrin receptors in the human gastrointestinal tract and pancreas. Gastroenterol Jpn. 1989;24:109–114.

    PubMed  CAS  Google Scholar 

  16. Ito M, Tanaka S, Maeda M, et al. Role of the gastrin–gastrin receptor system in the expansive growth of human gastric neoplasms. Digestion. 2008;78:163–170.

    Article  PubMed  CAS  Google Scholar 

  17. Suzuki H, Hibi T, Marshall BJ. Helicobacter pylori: present status and future prospects in Japan. J Gastroenterol. 2007;42:1–15.

    Article  PubMed  Google Scholar 

  18. Ito M, Takata S, Tatsugami M, et al. Clinical prevention of gastric cancer by Helicobacter pylori eradication therapy: a systematic review. J Gastroenterol. 2009;44:365–371.

    Article  PubMed  Google Scholar 

  19. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney system. International workshop on the histopathology of gastritis, Houston. Am J Surg Pathol. 1996;20:1161–1181.

    Article  PubMed  CAS  Google Scholar 

  20. Ito M, Tanaka S, Kim S, et al. A combination of the Helicobacter pylori stool antigen test and urea breath test is useful for clinical evaluation of eradication therapy: a multicenter study. J Gastroenterol Hepatol. 2005;20:1241–1245.

    Article  PubMed  Google Scholar 

  21. Yoshihara M, Sumii K, Haruma K, et al. Correlation of ratio of serum pepsinogen I and II with prevalence of gastric cancer and adenoma in Japanese subjects. Am J Gastroenterol. 1998;93:1090–1096.

    Article  PubMed  CAS  Google Scholar 

  22. Kulaksiz H, Arnold R, Goke B, et al. Expression and cell-specific localization of the cholecystokinin B/gastrin receptor in the human stomach. Cell Tissue Res. 2000;299:289–298.

    Article  PubMed  CAS  Google Scholar 

  23. Fukuhara H, Kadowaki Y, Ose T, et al. In vivo evidence for the role of RegI in gastric regeneration: transgenic overexpression of RegI accelerates the healing of experimental gastric ulcers. Lab Invest. 2010;90:556–565.

    Article  PubMed  CAS  Google Scholar 

  24. Ashurst HL, Varro A, Dimaline R. Regulation of mammalian gastrin/CCK receptor (CCK2R) expression in vitro and in vivo. Exp Physiol. 2008;93:223–236.

    Article  PubMed  CAS  Google Scholar 

  25. Haruma K, Yoshihara M, Sumii K, et al. Gastric acid secretion, serum pepsinogen I, and serum gastrin in Japanese with gastric hyperplastic polyps or polypoid-type early gastric carcinoma. Scand J Gastroenterol. 1993;28:633–637.

    Article  PubMed  CAS  Google Scholar 

  26. Hongo M, Gastric Polyps Study Group. Incidence and risk factor of fundic gland polyp and hyperplastic polyp in long-term proton pump inhibitor therapy: a prospective study in Japan. J Gastroenterol. 2010;45:618–624.

    Article  PubMed  CAS  Google Scholar 

  27. Phillipson M, Atuma C, Henriksnäs J, Holm L. The importance of mucus layers and bicarbonate transport in preservation of gastric juxtamucosal pH. Am J Physiol Gastrointest Liver Physiol. 2002;282:G211–G219.

    PubMed  CAS  Google Scholar 

  28. Wang TC, Dangler CA, Chen D, et al. Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer. Gastroenterology. 2000;118:36–47.

    Article  PubMed  CAS  Google Scholar 

  29. Takaishi S, Cui G, Frederick DM, et al. Synergistic inhibitory effects of gastrin and histamine receptor antagonists on Helicobacter-induced gastric cancer. Gastroenterology. 2005;128:1965–1983.

    Article  PubMed  CAS  Google Scholar 

  30. Fukui T, Nishio A, Okazaki K, et al. Gastric mucosal hyperplasia via upregulation of gastrin induced by persistent activation of gastric innate immunity in major histocompatibility complex class II deficient mice. Gut. 2006;55:607–615.

    Article  PubMed  CAS  Google Scholar 

  31. Kawasaki D, Emori Y, Eta R, et al. Effect of Z-360, a novel orally active CCK-2/gastrin receptor antagonist on tumor growth in human pancreatic adenocarcinoma cell lines in vivo and mode of action determinations in vitro. Cancer Chemother Pharmacol. 2008;61:883–892.

    Article  PubMed  CAS  Google Scholar 

  32. Savage K, Waller HA, Stubbs M, et al. Targeting of cholecystokinin B/gastrin receptor in colonic, pancreatic and hepatocellular carcinoma cell lines. Int J Oncol. 2006;29:1429–1435.

    PubMed  CAS  Google Scholar 

  33. Graham DY, Asaka M. Eradication of gastric cancer and more efficient gastric cancer surveillance in Japan: two peas in a pod. J Gastroenterol. 2010;45:1–8.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Metabolism, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Akemi Takamura, Masanori Ito, Tomoyuki Boda, Yoko Matsumoto & Kazuaki Chayama

  2. Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan

    Shinji Tanaka

  3. Health Service Center, Hiroshima University, Higashi-Hiroshima, Japan

    Masaharu Yoshihara

Authors
  1. Akemi Takamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masanori Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomoyuki Boda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoko Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shinji Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masaharu Yoshihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kazuaki Chayama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masanori Ito.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takamura, A., Ito, M., Boda, T. et al. High Expression of Gastrin Receptor Protein in Injured Mucosa of Helicobacter pylori-Positive Gastritis. Dig Dis Sci 58, 634–640 (2013). https://doi.org/10.1007/s10620-012-2427-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-012-2427-6

Keywords

Search

Navigation