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Original article
Helicobacter pylori CagL dependent induction of gastrin expression via a novel αvβ5-integrin–integrin linked kinase signalling complex
  1. Tobias Wiedemann1,
  2. Stefan Hofbaur1,
  3. Nicole Tegtmeyer2,
  4. Sylwia Huber3,
  5. Norbert Sewald3,
  6. Silja Wessler4,
  7. Steffen Backert2,
  8. Gabriele Rieder1,4
  1. 1Ludwig Maximilians University Munich, Munich, Germany
  2. 2School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
  3. 3Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, Bielefeld, Germany
  4. 4Division of Molecular Biology, Department of Microbiology, University of Salzburg, Salzburg, Austria
  1. Correspondence to Dr G Rieder, Division of Molecular Biology, Department of Microbiology, University of Salzburg, Billrothstrasse 11, A-5020 Salzburg, Austria; gabriele.rieder{at}sbg.ac.at

Abstract

Objective One of the most important hormones in the human stomach is the peptide gastrin. It is mainly required for the regulation of gastric pH but is also involved in growth and differentiation of gastric epithelial cells. In Helicobacter pylori infected patients, gastrin secretion can be upregulated by the pathogen, resulting in hypergastrinaemia. H pylori induced hypergastrinaemia is described as being a major risk factor for the development of gastric adenocarcinoma.

Design In this study, the upstream receptor complex and bacterial factors involved in H pylori induced gastrin gene expression were investigated, utilising gastric epithelial cells which were stably transfected with a human gastrin promoter luciferase reporter construct.

Results Integrin linked kinase (ILK) and integrin β5, but not integrin β1, played an important role in gastrin promoter activation. Interestingly, a novel CagL/integrin β5/ILK signalling complex was characterised as being important for H pylori induced gastrin expression. On interaction of H pylori with αvβ5-integrin and ILK, the epidermal growth factor receptor (EGFR) →Raf→mitogen activated protein kinase kinase (MEK)→extracellular signal regulated kinase (Erk) downstream signalling cascade was identified which plays a central role in H pylori gastrin induction.

Conclusion The newly discovered recognition receptor complex could be a useful target in treating precancerous conditions triggered by H pylori induced hypergastrinaemia.

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Footnotes

  • Funding The work was supported by Deutsche Forschungsgemeinschaft (DFG) RI 972/3-1 to GR and Ba1671/8-1 to SB.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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