Basic–alimentary tractThe Role of Matrix Metalloproteinase-7 in Redefining the Gastric Microenvironment in Response to Helicobacter pylori
Section snippets
Cells and Drugs
Human gastric glands and myofibroblasts were prepared as described later. Human recombinant MMP-7, MMP-7 antisense oligonucleotides, control oligonucleotides, MMP-7 fluorogenic substrate, and human collagen IV were obtained from Calbiochem (Nottingham, UK). Human recombinant IGFBP-5, IGF-II, and neutralizing IGF-II antibody were obtained from R&D Systems (Abingdon, Oxon, UK). All other chemicals were obtained from Sigma (Poole, Dorset, UK).
Patients
Endoscopic pinch biopsy specimens of gastric corpus
Increased Abundance of α-SMA in Human and Mouse Stomach With Helicobacter Infection
In initial studies we asked whether there is an increased abundance of the myofibroblast marker α-SMA in the corpus of Helicobacter-infected stomachs. In samples from H pylori–infected patients, densitometric analysis of Western blots revealed a significant increase in the abundance of α-SMA (Figure 1A and B). Immunohistochemistry for α-SMA in infected gastric corpus mucosa indicated the presence of myofibroblasts at all levels including around the neck region of the gastric glands, whereas
Discussion
The present study shows that in Helicobacter pylori infection there is increased abundance of the myofibroblast marker α-SMA in the gastric mucosa. We identify a role for MMP-7 derived from gastric epithelial cells as a myofibroblast growth factor acting via cleavage of IGFBP-5 to liberate IGF-II. MMP-7 does not (on its own) stimulate epithelial cell proliferation. However, IGF-II stimulates gastric epithelial cell proliferation, and medium from MMP-7–treated myofibroblasts stimulates
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Supported by North West Cancer Research Fund, the Medical Research Council, and the Wellcome Trust.