title: Up-regulated Smad5 mediates apoptosis of gastric epithelial cells induced by Helicobacter pylori infection.
abstract: The gastric pathogen Helicobacter pylori activates epithelial cell signaling pathways, and its infection induces changes in the expression of several genes in infected human gastric tissues. Recent studies have indicated that the ability of H. pylori to regulate epithelial cell responses depends on the presence of an intact cag pathogenicity island (cagPAI). We investigated altered mRNA expression of gastric epithelial cells after infection with H. pylori, both cagPAI-positive and cagPAI-negative strains, by cDNA microarray, reverse transcription PCR, and Northern blot analysis. Our results indicated that cagPAI-positive H. pylori strains (ATCC 43504 and clinical isolated strains) significantly activated Smad5 mRNA expression of human gastric epithelial cells (AGS, KATOIII, MKN28, and MKN45). We further examined whether the up-regulated Smad5 was related to apoptosis of gastric epithelial cells induced by H. pylori. Smad5 RNA interference completely inhibited H. pylori-induced apoptosis. These results suggest that Smad5 is up-regulated in gastric epithelial cells through the presence of cagPAI of H. pylori and that Smad5 mediates apoptosis of gastric epithelial cells induced by H. pylori infection.
authors.affiliation: Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Nagasako
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Takuji
authors.initials: T
authors.lastname: Mizushima
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Miura
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Kato
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D016481:Helicobacter Infections / Q000378:metabolism / Q000473:pathology*; D016480:Helicobacter pylori; D006801:Humans; D010750:Phosphoproteins / Q000096:biosynthesis*; D015398:Signal Transduction; D051902:Smad5 Protein; D015534:Trans-Activators / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D010750:Phosphoproteins; C497797:SMAD5 protein, human; D051902:Smad5 Protein; D015534:Trans-Activators