Helicobacter pylori induces beta 3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl-Lewis x

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

Marcos, NT (Autor) Outra; Magalhaes, A (Autor) Outra; Ferreira, B (Autor) Outra; Oliveira, MJ (Autor) FMUP; Carvalho, AS (Autor) Outra; Mendes, N (Autor) Outra; Gilmartin, T (Autor) Outra; Head, SR (Autor) Outra; Figueiredo C (Autor) FMUP; David L (Autor) FMUP; Santos-Silva F (Autor) FMUP; Celso Reis (Autor) FMUP

Revista

Título: Journal of Clinical Investigation

Vol. 118

Páginas: 2325-2336

ISSN: 0021-9738

Editora: American Society for Clinical Investigation

Indexação

ISI Web of Knowledge - 95 Citações

Scopus - 102 Citações

Outras Informações

ID Authenticus: P-003-Z09

DOI: 10.1172/jc134324

Abstract (EN): Chronic Helicobacter pylori infection is recognized as a cause of gastric cancer. H. pylori adhesion to gastric cells is mediated by bacterial adhesins such as sialic acid-binding adhesin (SabA), which binds the carbohydrate structure sialyl-Lewis x. Sialyl-Lewis x expression in the gastric epithelium is induced during persistent H. pylori infection, suggesting that H. pylori modulates host cell glycosylation patterns for enhanced adhesion. Here, we evaluate changes in the glycosylation-related gene expression profile of a human gastric carcinoma cell line following H. pylori infection. We observed that H. pylori significantly altered expression of 168 of the 1,031 human genes tested by microarray, and the extent of these alterations was associated with the pathogenicity of the H. pylori strain. A highly pathogenic strain altered expression of several genes involved in glycan biosynthesis, in particular that encoding beta 3 GlcNAc T5 (beta 3GnT5), a GlcNAc transferase essential for the biosynthesis of Lewis antigens. beta 3GnT5 induction was specific to infection with highly pathogenic strains of H. pylori carrying a cluster of genes known as the cag pathogenicity island, and was dependent on CagA and CagE. Further, beta 3GnT5 overexpression in human gastric carcinoma cell lines led to increased sialyl-Lewis x expression and H. pylori adhesion. This study identifies what we believe to be a novel mechanism by which H. pylori modulates the biosynthesis of the SabA ligand in gastric cells, thereby strengthening the epithelial attachment necessary to achieve successful colonization.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12