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Helicobacter pylori stimulates gastric epithelial cell MMP-1 secretion via CagA-dependent and -independent ERK

Michael H Pillinger1, Nada Marjanovic, Seok-Yong Kim

  • 1Department of Medicine, New York University School of Medicine, New York, New York 10016, USA. michael.pillinger@med.nyu.edu

The Journal of Biological Chemistry
|May 4, 2007
PubMed

Insights

Helicobacter pylori infection stimulates matrix metalloproteinase-1 (MMP-1) secretion, a key factor in gastric injury. The CagA protein, a virulence factor, plays a significant role in this MMP-1 secretion process.

Area of Science:

  • Gastroenterology
  • Microbiology
  • Molecular Biology

Background:

  • Mechanisms of Helicobacter pylori-induced gastric injury remain unclear.
  • H. pylori may disrupt gastric stroma by inducing matrix metalloproteinase-1 (MMP-1) secretion.
  • The role of the H. pylori virulence factor CagA in MMP-1 secretion requires further investigation.

Purpose of the Study:

  • To investigate the hypothesis that H. pylori induces MMP-1 secretion, potentially disrupting the gastric stroma.
  • To determine the role of the H. pylori virulence factor CagA in regulating MMP-1 secretion.

Main Methods:

  • Co-incubation of AGS cells with different H. pylori strains (cagA-positive and cagA-negative).
  • Transfection of cells with recombinant cagA genes.
  • Analysis of MMP-1 secretion and MAP kinase (ERK, p38) activation.
  • Inhibition studies using MEK and p38 inhibitors.

Main Results:

  • H. pylori stimulated MMP-1 secretion independently of CagA.
  • CagA translocation into AGS cells increased MMP-1 secretion.
  • CagA tyrosine phosphorylation regulates MMP-1 secretion.
  • H. pylori activated ERK in a CagA-independent (early) and -dependent (later) manner.
  • MEK inhibitors blocked MMP-1 secretion, while p38 inhibition enhanced it, suggesting p38 negatively regulates MMP-1 and ERK.

Conclusions:

  • H. pylori induces gastric epithelial MMP-1 expression.
  • The mitogen-activated protein kinase ERK is a key mediator of H. pylori-induced MMP-1 secretion.
  • CagA plays a significant role in modulating this signaling pathway.
  • p38 kinase may act as a negative regulator in this system.

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