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PLoS Pathog:发现对胃溃疡起重要防御作用的蛋白质

来源:生命经纬 2009-10-15 08:02

哥德堡大学萨尔格学院的研究人员在胃部发现了一种特殊的蛋白质,该蛋白质对机体抵抗幽门螺旋杆菌(Helicobacter  pylori)引起的胃溃疡起着重要防御作用。这项发现或许能够解释为什么幽门螺旋杆菌使某些人比其他人更易患病的原因。这篇研究报告发表在PLoS Pathogens杂志上。

据研究人员Sara  Lindén介绍,大约有一半的人胃部都携带有幽门螺旋杆菌,而这些人中只有少部分人出现胃溃疡或是胃癌。研究人员在胃部发现一种命名为MUC1的蛋白质,该蛋白质能够对幽门螺旋杆菌的起到防御作用。胃部表面的MUC1蛋白的结构类似于“从低矮的灌木丛长出的一棵大树”,因此,当幽门螺旋杆菌与MUC1蛋白连接后,该细菌就很少能够感染胃壁细胞。但是由于人与人之间由于遗传变异作用,使得MUC1蛋白质分子的长度因人而异,所以这或许是幽门螺旋杆菌对某些人更具有致病性的原因。(生物谷Bioon.com)

生物谷推荐原始出处:

PLoS Pathog 5(10): e1000617. doi:10.1371/journal.ppat.1000617

MUC1 Limits Helicobacter pylori Infection both by Steric Hindrance and by Acting as a Releasable Decoy

Sara K. Lindén1,2*, Yong H. Sheng1, Alison L. Every3, Kim M. Miles1, Emma C. Skoog2, Timothy H. J. Florin1,4, Philip Sutton3, Michael A. McGuckin1*

1 Mucosal Diseases Program, Mater Medical Research Institute, Mater Health Services, South Brisbane, Queensland, Australia, 2 Mucosal Immunobiology and Vaccine Center, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden, 3 Centre for Animal Biotechnology, School of Veterinary Science, University of Melbourne, Melbourne, Victoria, Australia, 4 Department of Medicine, University of Queensland, Queensland, Australia

The bacterium Helicobacter pylori can cause peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. The cell-surface mucin MUC1 is a large glycoprotein which is highly expressed on the mucosal surface and limits the density of H. pylori in a murine infection model. We now demonstrate that by using the BabA and SabA adhesins, H. pylori bind MUC1 isolated from human gastric cells and MUC1 shed into gastric juice. Both H. pylori carrying these adhesins, and beads coated with MUC1 antibodies, induced shedding of MUC1 from MKN7 human gastric epithelial cells, and shed MUC1 was found bound to H. pylori. Shedding of MUC1 from non-infected cells was not mediated by the known MUC1 sheddases ADAM17 and MMP-14. However, knockdown of MMP-14 partially affected MUC1 release early in infection, whereas ADAM17 had no effect. Thus, it is likely that shedding is mediated both by proteases and by disassociation of the non-covalent interaction between the α- and β-subunits. H. pylori bound more readily to MUC1 depleted cells even when the bacteria lacked the BabA and SabA adhesins, showing that MUC1 inhibits attachment even when bacteria cannot bind to the mucin. Bacteria lacking both the BabA and SabA adhesins caused less apoptosis in MKN7 cells than wild-type bacteria, having a greater effect than deletion of the CagA pathogenicity gene. Deficiency of MUC1/Muc1 resulted in increased epithelial cell apoptosis, both in MKN7 cells in vitro, and in H. pylori infected mice. Thus, MUC1 protects the epithelium from non-MUC1 binding bacteria by inhibiting adhesion to the cell surface by steric hindrance, and from MUC1-binding bacteria by acting as a releasable decoy.

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