Gastrin stimulates MMP-1 expression in gastric epithelial cells

Putative role in gastric epithelial cell migration

J. Dinesh Kumar, Islay Steele, Andrew R. Moore, Senthil V. Murugesan, Z. Rakonczay, V. Venglovecz, D. Mark Pritchard, Rodney Dimaline, L. Tiszlavicz, Andrea Varro, Graham J. Dockray

Research output: Contribution to journalArticle

14 Citations (Scopus)

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. Gastrinstimulated 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.

Original languageEnglish
Pages (from-to)G78-G86
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume309
Issue number2
DOIs
Publication statusPublished - Jul 15 2015

Fingerprint

Matrix Metalloproteinase 1
Gastrins
Cell Movement
Stomach
Epithelial Cells
Proton Pump Inhibitors
Western Blotting
Matrix Metalloproteinase 7
Cholecystokinin Receptors
Matrix Metalloproteinase 3
Mitogen-Activated Protein Kinase 1
Serum
Helicobacter pylori
Protein Kinase C
Histology
Epithelium
Hormones
Biopsy

Keywords

  • Gastric epithelium
  • Gastrin
  • MMP-1

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Gastrin stimulates MMP-1 expression in gastric epithelial cells : Putative role in gastric epithelial cell migration. / Kumar, J. Dinesh; Steele, Islay; Moore, Andrew R.; Murugesan, Senthil V.; Rakonczay, Z.; Venglovecz, V.; Pritchard, D. Mark; Dimaline, Rodney; Tiszlavicz, L.; Varro, Andrea; Dockray, Graham J.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 309, No. 2, 15.07.2015, p. G78-G86.

Research output: Contribution to journalArticle

Kumar, J. Dinesh ; Steele, Islay ; Moore, Andrew R. ; Murugesan, Senthil V. ; Rakonczay, Z. ; Venglovecz, V. ; Pritchard, D. Mark ; Dimaline, Rodney ; Tiszlavicz, L. ; Varro, Andrea ; Dockray, Graham J. / Gastrin stimulates MMP-1 expression in gastric epithelial cells : Putative role in gastric epithelial cell migration. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2015 ; Vol. 309, No. 2. pp. G78-G86.
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