title: Stimulation of MMP-7 (matrilysin) by Helicobacter pylori in human gastric epithelial cells: role in epithelial cell migration.
abstract: 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-kappaB and AP-1, whereas Rac activated NF-kappaB 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.
authors.affiliation: Physiological Laboratory, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Lydia E
authors.initials: LE
authors.lastname: Wroblewski
authors.forename: P-J M
authors.initials: PJ
authors.lastname: Noble
authors.forename: Adelina
authors.initials: A
authors.lastname: Pagliocca
authors.forename: D Mark
authors.initials: DM
authors.lastname: Pritchard
authors.forename: C Anthony
authors.initials: CA
authors.lastname: Hart
authors.forename: Fiona
authors.initials: F
authors.lastname: Campbell
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Dodson
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Dockray
authors.forename: Andrea
authors.initials: A
authors.lastname: Varro
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology* / Q000201:enzymology; D005753:Gastric Mucosa / Q000378:metabolism*; D017930:Genes, Reporter; D005822:Genetic Vectors; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011863:Radioimmunoassay; D015398:Signal Transduction; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D008156:Luciferases; D020783:Matrix Metalloproteinase 7; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein