McCaig, C, Duval, C, Hemers, E et al. (10 more authors) (2006) The role of matrix metalloproteinase-7 in redefining the gastric microenvironment in response to Helicobacter pylori. Gastroenterology, 130 (6). 1754 - 1763. ISSN 0016-5085
Abstract
BACKGROUND & AIMS: Interactions between epithelial and stromal cells are important determinants of mucosal organization, but the signaling mechanisms are understood incompletely. Matrix metalloproteinase (MMP)-7 is produced uniquely in epithelia, may act on growth factors and matrix proteins, and in the stomach is increased with Helicobacter pylori infection. We have studied the role of MMP-7 in signaling between epithelial cells and a key stromal cell type, the myofibroblast. METHODS: Immunohistochemistry and Western blotting were applied to gastric corpus biopsy specimens; primary cultures of human gastric glands and myofibroblasts were used to study the role of MMP-7 in regulating proliferation and migration of the latter, and MMP-7 substrates were identified by proteomic methods. RESULTS: Increased abundance of the myofibroblast marker alpha-smooth muscle actin was identified in H. pylori-positive biopsy specimens. Media from H pylori-infected gastric epithelial cultures stimulated proliferation and migration of primary human gastric myofibroblasts and antisense oligonucleotide treatment indicated a role for MMP-7. Proteomic methods identified insulin-like growth factor binding protein (IGFBP)-5 as a substrate for MMP-7 in medium from gastric myofibroblasts. Knockdown of IGFBP-5 by small interfering RNA or immunoneutralization of IGF-II, abolished myofibroblast responses to MMP-7. Proliferation of gastric epithelial cells also was stimulated by MMP-7-treated myofibroblasts via IGF-II. CONCLUSIONS: MMP-7 acts as an epithelial-derived signal increasing the bioavailability of IGF-II released from myofibroblasts. Because IGF-II acts on both stromal and epithelial cells, the findings suggest that increased MMP-7 expression contributes to redefining the niche occupied by dividing cells and leading to hyperproliferation in H pylori infection.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Animals; biopsy, needle; blotting, western; cell proliferation; cells, cultured; disease models, animal; fibroblasts; gastric mucosa; gastrins; helicobacter infections; helicobacter pylori; humans; immunohistochemistry; male; matrix metalloproteinase 7; mice; probability; radioimmunoassay; sensitivity and specificity |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Academic Unit of Cardiovascular Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Mar 2015 11:22 |
Last Modified: | 03 Nov 2016 17:39 |
Published Version: | http://dx.doi.org/10.1053/j.gastro.2006.02.031 |
Status: | Published |
Publisher: | WB Saunders |
Identification Number: | 10.1053/j.gastro.2006.02.031 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:83629 |