Stimulation of MMP-7 (matrilysin) byHelicobacter pyloriin human gastric epithelial cells: role in epithelial cell migration
| Autor: | Peter J. M. Noble, Fiona Campbell, Andrea Varro, Adelina Pagliocca, Graham J. Dockray, Lydia E. Wroblewski, C. Anthony Hart, Andrew Dodson, D. Mark Pritchard |
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| Rok vydání: | 2003 |
| Předmět: |
Time Factors
RHOA Blotting Western Genetic Vectors Radioimmunoassay Transfection Epithelial cell migration Microbiology Cell Movement Genes Reporter Cell Line Tumor Gastric glands medicine Humans Neoplasm Invasiveness Enterochromaffin-like cell Matrilysin Luciferases Promoter Regions Genetic Cells Cultured Helicobacter pylori biology Stomach NF-kappa B Epithelial Cells Cell Biology Oligonucleotides Antisense biology.organism_classification Immunohistochemistry Up-Regulation rac GTP-Binding Proteins Transcription Factor AP-1 Rac GTP-Binding Proteins medicine.anatomical_structure Gastric Mucosa Matrix Metalloproteinase 7 Cancer research biology.protein rhoA GTP-Binding Protein Plasmids Signal Transduction Transcription Factors |
| Zdroj: | Journal of Cell Science. 116:3017-3026 |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Epithelial cell responses to bacterial infection include induction of matrix metalloproteinase 7 (MMP-7). Here, we identify increased MMP-7 expression in the gastric epithelium in response to the oncogenic bacterium Helicobacter pylori, and report on the mechanisms and consequences for gastric epithelial cell migration. In patients infected with H. pylori, there was increased MMP-7 in gastric biopsies detected by western blot. MMP-7 was localized to the advancing edge of migrating gastric epithelial cell colonies, including lamellipodia. Rates of spreading of gastric gland cells were higher in H. pylori-infected cultures compared with control, and this was inhibited by antisense oligonucleotides to MMP-7. Complementary data were obtained in a gastric cancer cell line (AGS cells). In the latter, H. pylori induced expression of an MMP-7-luciferase promoter/reporter vector through mechanisms that involved activation of Rho and Rac. RhoA acted through activation of both NF-κB and AP-1, whereas Rac activated NF-κB but not AP-1. MMP-7 is commonly upregulated in gastric cancer; since H. pylori is a recognized gastric carcinogen, the data suggest a new mechanism by which the bacterium might predispose towards gastric neoplasia. |
| Databáze: | OpenAIRE |
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