Helicobacter pylori strain-selective induction of matrix metalloproteinase-7 in vitro and within gastric mucosa

Howard C. Crawford, Uma S. Krishna, Dawn A. Israel, Lynn M. Matrisian, M. Kay Washington, Richard M. Peek

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92 Scopus citations

Abstract

Background & Aims: Helicobacter pylori strains that possess the cag pathogenicity island (cag+) augment the risk for distal gastric cancer. Matrix metalloproteinase (MMP)-7, an epithelial cell-derived MMP that is induced by bacterial contact, is overexpressed within human gastric adenocarcinoma specimens and enhances tumor formation in rodents. We determined whether H. pylori alters MMP-7 expression and investigated the molecular pathways required for these events. Methods: MMP-7 was detected in human gastric mucosa by immunohistochemistry and in H. pylori/AGS gastric epithelial cell coculture supernatants by Western analysis. AGS cells were cocultured with wild-type H. pylori, or isogenic cagA-, cagE-, or vacA- mutants, in the absence or presence of inhibitors of nuclear factor κB activation, p38, or extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase. Results: H. pylori cag+ strains increased MMP-7 expression in AGS cells 5-7-fold, whereas cag- isolates had no effect. Inactivation of cagE, but not cagA or vacA, completely attenuated induction of MMP-7, and inhibition of ERK 1/2 decreased MMP-7 production. In vivo, MMP-7 was expressed in gastric epithelial cells in specimens from 80% of cag+-colonized persons but in none of the cag- or uninfected subjects. Conclusions: H. pylori cag+ strains enhance levels of MMP-7 within inflamed mucosa. In vitro, cag + isolates selectively induce MMP-7, and this is dependent on activation of ERK 1/2 by specific components within the cag island. Differential induction of MMP-7 by H. pylori cag+ isolates may explain in part the augmentation in gastric cancer risk associated with these strains.

Original languageEnglish (US)
Pages (from-to)1125-1136
Number of pages12
JournalGastroenterology
Volume125
Issue number4
DOIs
StatePublished - Oct 1 2003

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Crawford, H. C., Krishna, U. S., Israel, D. A., Matrisian, L. M., Washington, M. K., & Peek, R. M. (2003). Helicobacter pylori strain-selective induction of matrix metalloproteinase-7 in vitro and within gastric mucosa. Gastroenterology, 125(4), 1125-1136. https://doi.org/10.1016/S0016-5085(03)01206-X