Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA of Helicobacter pylori
Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA of Helicobacter pylori
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DOI：
10.1038/ng1112
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发表时间：
2003-03-01
期刊：
影响因子：
30.8
通讯作者：
Noda, M
中科院分区：
文献类型：
--
作者：
Fujikawa, A;Shirasaka, D;Noda, M
幽门螺杆菌产生的空泡化细胞毒素VacA在体外会引起大量的细胞空泡化(1-3)，在体内会引起胃组织损伤，导致胃溃疡。在这里，我们报告了蛋白酪氨酸磷酸酶受体Z(Ptprz，也称为PTP-XI或RPTP-β，由Ptprz编码)缺陷小鼠没有表现出VacA对粘膜的损害，尽管VacA与野生型小鼠一样被掺入胃上皮细胞。原代培养的Ptprz(+/+)和Ptprz(-/-)小鼠的胃上皮细胞也显示出相似的VacA掺入、细胞空泡化和细胞增殖减少，但仅Ptprz(+/+)细胞在VacA处理后24 h显示明显脱离重组基底膜。VacA与Ptprz结合，并且Ptprz底物G蛋白偶联受体激酶相互作用蛋白1(Git1)的酪氨酸磷酸化水平在VacA处理后升高，表明VacA是Ptprz的配体。此外，Ptprz的内源性配体多营养素(PTN)在口服时也能特异性地诱导Ptprz(+/+)小鼠的胃炎。综上所述，这些数据表明错误的Ptprz信号会导致胃溃疡。
The vacuolating cytotoxin VacA produced by Helicobacter pylori causes massive cellular vacuolation in vitro(1-3) and gastric tissue damage in vivo, leading to gastric ulcers, when administered intragastrically(4). Here we report that mice deficient in protein tyrosine phosphatase receptor type Z (Ptprz, also called PTP-xi or RPTP-beta, 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.