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Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA of Helicobacter pylori

A Corrigendum to this article was published on 01 April 2003

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Abstract

The vacuolating cytotoxin VacA produced by Helicobacter pylori causes massive cellular vacuolation in vitro1,2,3 and gastric tissue damage in vivo, leading to gastric ulcers, when administered intragastrically4. Here we report that mice deficient in protein tyrosine phosphatase receptor type Z (Ptprz, also called PTP-ζ or RPTP-β, encoded by Ptprz) do not show mucosal damage by VacA, although VacA is incorporated into the gastric epithelial cells to the same extent as in wild-type mice. Primary cultures of gastric epithelial cells from Ptprz+/+ and Ptprz−/− mice also showed similar incorporation of VacA, cellular vacuolation and reduction in cellular proliferation, but only Ptprz+/+ cells showed marked detachment from a reconstituted basement membrane 24 h after treatment with VacA. VacA bound to Ptprz, and the levels of tyrosine phosphorylation of the G protein–coupled receptor kinase–interactor 1 (Git1), a Ptprz substrate, were higher after treatment with VacA, indicating that VacA behaves as a ligand for Ptprz. Furthermore, pleiotrophin (PTN), an endogenous ligand of Ptprz, also induced gastritis specifically in Ptprz+/+ mice when administered orally. Taken together, these data indicate that erroneous Ptprz signaling induces gastric ulcers.

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Figure 1: Ptprz expression and VacA binding in the stomach.
Figure 2: Pathological analyses of gastric tissues treated with VacA.
Figure 3: Role of Ptprz in the virulence of VacA.
Figure 4: Effect of VacA on Ptprz signaling.
Figure 5: Effect of oral administration of PTN on gastric tissues.

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  • 04 March 2003

    Added the revised supplementary info (all six pieces were replaced)

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Acknowledgements

We thank T. Etoh, M. Mizoguchi, K. Yamada and M. Gotoh for technical assistance and A. Kodama for secretarial assistance. The BIAcore system was used at the NIBB Center for Analytical Instruments. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology and from Yamanouchi Foundation for Research on Metabolic Disorders and by Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation.

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Correspondence to Masaharu Noda.

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NOTE: The Supplementary Information for this paper originally published online was incorrect. We have since replaced it with the correct files. (PDF 129 kb)

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Fujikawa, A., Shirasaka, D., Yamamoto, S. et al. Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA of Helicobacter pylori. Nat Genet 33, 375–381 (2003). https://doi.org/10.1038/ng1112

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