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' @# I4 o' W4 @; g. yBacteria can break apart cell junctions that link neighboring stomach cells, based on the work of Manuel Amieva, Roger Vogelmann, Stanley Falkow (Stanford University, Stanford, CA), and colleagues. Although the bacteria may do it to gain access to tasty chemicals that leak out, the results for humans may include stomach ulcers and gastric cancer.
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The link from cell junctions to stomach ailments may, say the researchers, lie in tissue repair. Injury to the stomach triggers cell division and migration to plug the gap. The chiefs in charge of these processes may well lie in cell junctions〞ideally placed, as they would be, to sense whether there is a breach in the epithelium. If bacterial proteins interfere with that process, the persistent gaps could lead to ulcers. And if the bacterial proteins push the repair process into inappropriate overdrive then cancerous growths might arise.
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Such pathways remain the stuff of speculation. But what the Stanford team has shown is that CagA, a protein that the ulcer-associated bacterium Helicobacter pylori injects into gastric epithelial cells, can associate and interfere with junctional proteins. Some of the tight junction scaffolding protein ZO-1 is lured away from junctions to associate with attached bacteria, and still more ZO-1 colocalizes with intracellular CagA at the remaining tight junctions, which are now leaky.
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Others have demonstrated that CagA can bind signaling proteins such as SHP2 and Grb2 and increase spreading of isolated cells driven by the c-Met receptor. Although these effects are initially resisted in monolayers, the cells eventually succumb, perhaps when CagA induces inappropriate signaling from what is left of the cell junctions.
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Reference:
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Amieva, M.R., et al. 2003. Science. 300:1430–1434.(H. pylori (Hp) opens up cell junctions t) |
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发表于 2009-3-6 00:54
发表于 2015-5-25 14:16
