| RRC ID |
37076
|
| 著者 |
Kumar JD, Steele I, Moore AR, Murugesan SV, Rakonczay Z, Venglovecz V, Pritchard DM, Dimaline R, Tiszlavicz L, Varro A, Dockray GJ.
|
| タイトル |
Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration.
|
| ジャーナル |
Am J Physiol Gastrointest Liver Physiol
|
| 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.
|
| 巻・号 |
309(2)
|
| ページ |
G78-86
|
| 公開日 |
2015-7-15
|
| DOI |
10.1152/ajpgi.00084.2015
|
| PII |
ajpgi.00084.2015
|
| PMID |
25977510
|
| PMC |
PMC4504956
|
| MeSH |
Animals
Case-Control Studies
Cell Movement* / drug effects
Cells, Cultured
Epithelial Cells / drug effects
Epithelial Cells / enzymology*
Gastric Mucosa / drug effects
Gastric Mucosa / enzymology*
Gastrins / blood
Gastrins / genetics
Gastrins / metabolism*
Humans
Matrix Metalloproteinase 1 / genetics
Matrix Metalloproteinase 1 / metabolism*
Mice
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Protein Kinase C / metabolism
Proton Pump Inhibitors / pharmacology
RNA, Messenger / metabolism
Rats
Signal Transduction
Transfection
Up-Regulation
|
| IF |
3.725
|
| 引用数 |
14
|
|
WOS 分野
|
PHYSIOLOGY
GASTROENTEROLOGY & HEPATOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RGM1(RCB0876) |
