title: Helicobacter pylori CagL dependent induction of gastrin expression via a novel αvβ5-integrin-integrin linked kinase signalling complex.
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.
  
  
  METHODS
  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 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.
  
  
  CONCLUSIONS
  The newly discovered recognition receptor complex could be a useful target in treating precancerous conditions triggered by H pylori induced hypergastrinaemia.
authors.affiliation: Ludwig Maximilians University Munich, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Wiedemann
authors.forename: Stefan
authors.initials: S
authors.lastname: Hofbaur
authors.forename: Nicole
authors.initials: N
authors.lastname: Tegtmeyer
authors.forename: Sylwia
authors.initials: S
authors.lastname: Huber
authors.forename: Norbert
authors.initials: N
authors.lastname: Sewald
authors.forename: Silja
authors.initials: S
authors.lastname: Wessler
authors.forename: Steffen
authors.initials: S
authors.lastname: Backert
authors.forename: Gabriele
authors.initials: G
authors.lastname: Rieder
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D015870:Gene Expression; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology; D000099200:Scaffold Protein ILK
chemical_list: D001426:Bacterial Proteins; D005755:Gastrins; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C568315:cagL protein, Helicobacter pylori