{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:49:58Z","timestamp":1791020998913,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T00:00:00Z","timestamp":1220227200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Chronic infection with the gastric pathogen<jats:italic>Helicobacter pylori<\/jats:italic>significantly increases the risk of developing atrophic gastritis, peptic ulcer disease, and gastric adenocarcinoma.<jats:italic>H. pylori<\/jats:italic>strains that possess the<jats:italic>cag<\/jats:italic>pathogenicity island, which translocates CagA into the host cells, augment these risks. The aim of this study was to determine the molecular mechanisms through which<jats:italic>H. pylori<\/jats:italic>upregulates the expression of plasminogen activator inhibitor 1 (PAI-1), a member of the urokinase activator system that is involved in tumor metastasis and angiogenesis. Levels of PAI-1 mRNA and protein were examined in tissues from<jats:italic>H. pylori<\/jats:italic>-infected patients and in vitro using AGS gastric epithelial cells. In vitro, cells were infected with toxigenic<jats:italic>cag<\/jats:italic>-positive or nontoxigenic<jats:italic>cag<\/jats:italic>-negative strains of<jats:italic>H. pylori<\/jats:italic>or isogenic mutants. The amount of PAI-1 secretion was measured by enzyme-linked immunosorbent assay, and mRNA levels were determined using real-time PCR. The regulation of PAI-1 was examined using the extracellular signal-regulated kinase 1\/2 (ERK1\/2) inhibitor and small interfering RNA. Analysis of human biopsy samples revealed an increase in both PAI-1 mRNA and protein levels in patients with<jats:italic>H. pylori<\/jats:italic>gastritis compared to those of uninfected controls. Infection of AGS cells with<jats:italic>H. pylori<\/jats:italic>significantly increased PAI-1 mRNA expression and the secretion of PAI-1 protein. Moreover, PAI-1 mRNA and protein production was more pronounced when AGS cells were infected by<jats:italic>H. pylori<\/jats:italic>strains carrying a functional<jats:italic>cag<\/jats:italic>secretion system than when cells were infected by strains lacking this system. PAI-1 secretion was also reduced when cells were infected with either<jats:italic>cagE<\/jats:italic>-negative or<jats:italic>cagA<\/jats:italic>-negative mutants. The ectopic overexpression of CagA significantly increased the levels of PAI-1 mRNA and protein, whereas blockade of the ERK1\/2 pathway inhibited<jats:italic>H. pylori<\/jats:italic>-mediated PAI-1 upregulation. These findings suggest that the upregulation of PAI-1 in<jats:italic>H. pylori<\/jats:italic>-infected gastric epithelial cells may contribute to the carcinogenic process.<\/jats:p>","DOI":"10.1128\/iai.00584-08","type":"journal-article","created":{"date-parts":[[2008,6,3]],"date-time":"2008-06-03T00:57:02Z","timestamp":1212454622000},"page":"3992-3999","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["<i>Helicobacter pylori<\/i>Infection Stimulates Plasminogen Activator Inhibitor 1 Production by Gastric Epithelial Cells"],"prefix":"10.1128","volume":"76","author":[{"given":"A. 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