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http://purl.uniprot.org/citations/25658601http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25658601http://www.w3.org/2000/01/rdf-schema#comment"The cytotoxin-associated gene (Cag) pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori) that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD) CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat). Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylori that was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique approach to study H. pylori interaction with the human gastric epithelium. Here, we show that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.org/dc/terms/identifier"doi:10.1371/journal.ppat.1004663"xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Li J."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Peek R.M. Jr."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Schumacher M.A."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Feng R."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Boivin G.P."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Zavros Y."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Orian-Rousseau V."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Helmrath M.A."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Mahe M.M."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Engevik A.C."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Bertaux-Skeirik N."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Javier J.E."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/author"Ottemann K."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/name"PLoS Pathog"xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/pages"e1004663"xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/title"CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation."xsd:string
http://purl.uniprot.org/citations/25658601http://purl.uniprot.org/core/volume"11"xsd:string
http://purl.uniprot.org/citations/25658601http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25658601
http://purl.uniprot.org/citations/25658601http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25658601
http://purl.uniprot.org/uniprot/#_P15379-mappedCitation-25658601http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25658601
http://purl.uniprot.org/uniprot/#_A2APM1-mappedCitation-25658601http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25658601
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