title: Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration.
abstract: The pyloric antral hormone gastrin plays a role in remodeling of the gastric epithelium, but the specific targets of gastrin that mediate these effects are poorly understood. Glandular epithelial cells of the gastric corpus express matrix metalloproteinase (MMP)-1, which is a potential determinant of tissue remodeling; some of these cells express the CCK-2 receptor at which gastrin acts. We have now examined the hypothesis that gastrin stimulates expression of MMP-1 in the stomach. We determined MMP-1 transcript abundance in gastric mucosal biopsies from Helicobacter pylori negative human subjects with normal gastric mucosal histology, who had a range of serum gastrin concentrations due in part to treatment with proton pump inhibitors (PPI). The effects of gastrin were studied on gastric epithelial AGS-GR cells using Western blot and migration assays. In human subjects with increased serum gastrin due to PPI usage, MMP-1 transcript abundance was increased 2-fold; there was also increased MMP-7 transcript abundance but not MMP-3. In Western blots, gastrin increased proMMP-1 abundance, as well that of a minor band corresponding to active MMP-1, in the media of AGS-GR cells, and the response was mediated by protein kinase C and p42/44 MAP kinase. There was also increased MMP-1 enzyme activity. Gastrin-stimulated AGS-GR cell migration in both scratch wound and Boyden chamber assays was inhibited by MMP-1 immunoneutralization. We conclude that MMP-1 expression is a target of gastrin implicated in mucosal remodeling.
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and.
authors.forename: J Dinesh
authors.initials: JD
authors.lastname: Kumar
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and.
authors.forename: Islay
authors.initials: I
authors.lastname: Steele
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Moore
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and.
authors.forename: Senthil V
authors.initials: SV
authors.lastname: Murugesan
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Rakonczay
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Venglovecz
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and.
authors.forename: D Mark
authors.initials: DM
authors.lastname: Pritchard
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and.
authors.forename: Rodney
authors.initials: R
authors.lastname: Dimaline
authors.affiliation: Department of Pathology, University of Szeged, Szeged, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Tiszlavicz
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Varro
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and g.j.dockray@liverpool.ac.uk.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Dockray
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D005755:Gastrins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D005755:Gastrins; D054328:Proton Pump Inhibitors; D012333:RNA, Messenger; D011493:Protein Kinase C; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: MMP-1; gastric epithelium; gastrin