Bacterial cytotoxin induces the epithelial cell detachment that leads to ulcer formation.
Feb 23, 2003
Helicobacter pylori is a Gram-negative bacterium that colonizes the gut mucosa and can induce gastric ulcers. In an Advanced Online Publication in Nature Genetics, Akihiro Fujikawa and colleagues report how the H. pylori cytotoxin VacA causes ulcer formation (Nature Genetics, DOI:10.1038/ng1112, 24 February, 2003).
Mice lacking the Prptz gene — encoding a protein tyrosine phosphatase receptor type 2 expressed in gastric glands — are resistant to VacA-induced ulcers. VacA is taken up equally well by epithelial cells, in culture or in vivo, in the absence of Prptz, with no differences in vacuole development or cell survival. However, VacA binding to Ptprz initiates a signaling cascade that leads to cell detachment from the basement membrane. In addition, this can be mimicked with an endogenous Ptprz ligand that was also found to induce severe gastritis.
These findings indicate potential novel clinical strategies based on inhibiting the VacA-Ptprz...
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