title: Helicobacter pylori cag pathogenicity island-positive strains induce syndecan-4 expression in gastric epithelial cells.
abstract: Helicobacter pylori is recognized as the main cause of gastritis and is associated with gastric carcinogenesis. Syndecan-4 represents the major source of heparan sulfate (HS) in the gastric cells. HS proteoglycans expressed on the cell surface constitute targets for H. pylori at the early stage of infection. The aim of this study was to determine whether H. pylori induction of syndecan-4 expression is affected by the virulence characteristics of the infecting strain, namely the cytotoxic-associated gene (cag) pathogenicity island (PAI). We observed that individuals infected with highly pathogenic H. pylori strains express syndecan-4 in the foveolar epithelium of the gastric mucosa. The association between the cagPAI status of the infecting strain and syndecan-4 expression was further demonstrated by infection of gastric epithelial cell lines with a panel of cagPAI(+) and cagPAI(-)H. pylori strains, showing that expression of syndecan-4 was significantly increased in response to infection with the highly pathogenic strains. Moreover, infection of gastric cells with cagA and cagE mutant strains further confirmed that syndecan-4 induction is dependent on an intact cagPAI. The present study shows that highly pathogenic H. pylori strains induce syndecan-4 expression, both in human gastric mucosa and in gastric cell lines, in a cagPAI-dependent manner.
authors.affiliation: Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), 4200-465 Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Magalhães
authors.forename: Nuno T
authors.initials: NT
authors.lastname: Marcos
authors.forename: Ana S
authors.initials: AS
authors.lastname: Carvalho
authors.forename: Leonor
authors.initials: L
authors.lastname: David
authors.forename: Céu
authors.initials: C
authors.lastname: Figueiredo
authors.forename: Joana
authors.initials: J
authors.lastname: Bastos
authors.forename: Guido
authors.initials: G
authors.lastname: David
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics; D004847:Epithelial Cells / Q000382:microbiology*; D005753:Gastric Mucosa / Q000473:pathology; D020869:Gene Expression Profiling; D044404:Genomic Islands; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D053671:Syndecan-4 / Q000096:biosynthesis*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C508304:SDC4 protein, human; D053671:Syndecan-4; C080866:cagA protein, Helicobacter pylori