Helicobacter pylori CagL dependent induction of gastrin expression via a novel αvβ 5-integrineintegrin linked kinase signalling complex
Wiedemann T, Hofbaur S, Tegtmeyer N, Huber S, Sewald N, Wessler S, Backert S, Rieder G (2012)
Publication Type: Journal article
Publication year: 2012
Journal
Book Volume: 61
Pages Range: 986-996
Journal Issue: 7
DOI: 10.1136/gutjnl-2011-300525
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 b5, 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 αvβ 5-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.
Authors with CRIS profile
Involved external institutions
University College Dublin (UCD)
Ireland (IE)
Universität Salzburg (Paris Lodron Universität Salzburg)
Austria (AT)
Universität Bielefeld
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Ireland (IE)
Universität Salzburg (Paris Lodron Universität Salzburg)
Austria (AT)
Universität Bielefeld
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
How to cite
APA:
Wiedemann, T., Hofbaur, S., Tegtmeyer, N., Huber, S., Sewald, N., Wessler, S.,... Rieder, G. (2012). Helicobacter pylori CagL dependent induction of gastrin expression via a novel αvβ 5-integrineintegrin linked kinase signalling complex. Gut, 61(7), 986-996. https://doi.org/10.1136/gutjnl-2011-300525
MLA:
Wiedemann, Tobias, et al. "Helicobacter pylori CagL dependent induction of gastrin expression via a novel αvβ 5-integrineintegrin linked kinase signalling complex." Gut 61.7 (2012): 986-996.
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