PMID- 25977510 OWN - NLM STAT- MEDLINE DCOM- 20150928 LR - 20181113 IS - 1522-1547 (Electronic) IS - 0193-1857 (Print) IS - 0193-1857 (Linking) VI - 309 IP - 2 DP - 2015 Jul 15 TI - Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration. PG - G78-86 LID - 10.1152/ajpgi.00084.2015 [doi] AB - 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. CI - Copyright (c) 2015 the American Physiological Society. FAU - Kumar, J Dinesh AU - Kumar JD AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and. FAU - Steele, Islay AU - Steele I AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and. FAU - Moore, Andrew R AU - Moore AR AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and. FAU - Murugesan, Senthil V AU - Murugesan SV AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and. FAU - Rakonczay, Zoltan AU - Rakonczay Z AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and. FAU - Venglovecz, Viktoria AU - Venglovecz V AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and. FAU - Pritchard, D Mark AU - Pritchard DM AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and. FAU - Dimaline, Rodney AU - Dimaline R AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and. FAU - Tiszlavicz, Laszlo AU - Tiszlavicz L AD - Department of Pathology, University of Szeged, Szeged, Hungary. FAU - Varro, Andrea AU - Varro A AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and. FAU - Dockray, Graham J AU - Dockray GJ AD - Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and g.j.dockray@liverpool.ac.uk. LA - eng GR - Department of Health/United Kingdom GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150514 PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 RN - 0 (Gastrins) RN - 0 (Proton Pump Inhibitors) RN - 0 (RNA, Messenger) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.24 (MAPK1 protein, human) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 3.4.24.7 (MMP1 protein, human) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Animals MH - Case-Control Studies MH - *Cell Movement/drug effects MH - Cells, Cultured MH - Epithelial Cells/drug effects/*enzymology MH - Gastric Mucosa/drug effects/*enzymology MH - Gastrins/blood/genetics/*metabolism MH - Humans MH - Matrix Metalloproteinase 1/genetics/*metabolism MH - Mice MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Protein Kinase C/metabolism MH - Proton Pump Inhibitors/pharmacology MH - RNA, Messenger/metabolism MH - Rats MH - Signal Transduction MH - Transfection MH - Up-Regulation PMC - PMC4504956 OTO - NOTNLM OT - MMP-1 OT - gastric epithelium OT - gastrin EDAT- 2015/05/16 06:00 MHDA- 2015/09/29 06:00 PMCR- 2016/07/15 CRDT- 2015/05/16 06:00 PHST- 2015/03/13 00:00 [received] PHST- 2015/05/06 00:00 [accepted] PHST- 2015/05/16 06:00 [entrez] PHST- 2015/05/16 06:00 [pubmed] PHST- 2015/09/29 06:00 [medline] PHST- 2016/07/15 00:00 [pmc-release] AID - ajpgi.00084.2015 [pii] AID - GI-00084-2015 [pii] AID - 10.1152/ajpgi.00084.2015 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2015 Jul 15;309(2):G78-86. doi: 10.1152/ajpgi.00084.2015. Epub 2015 May 14.