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Updated: Mar 25, 2026

Mouse- and Human-derived Primary Gastric Epithelial Monolayer Culture for the Study of Regeneration
Published on: May 7, 2018
Helicobacter pylori-elicited induction in gastric mucosal matrix metalloproteinase-9 (MMP-9) release involves
1Research Center, C875, Rutgers School of Dental Medicine, Rutgers, The State University of New Jersey, 110 Bergen Street, PO Box 1709, Newark, NJ, 07103-2400, USA. slomiabr@sdm.rutgers.edu.
Abstract:
Matrix metalloproteinases (MMPs) are a family of endopeptidases implicated in a wide rage of degenerative and inflammatory diseases, including Helicobacter pylori-associated gastritis, and gastric and duodenal ulcer. As gastric mucosal inflammatory responses to H. pylori are characterized by the rise in MMP-9 production, as well as the induction in mitogen-activated protein kinase (MAPK) and Rac1 activation, we investigated the role of Rac1/MAPK in the processes associated with the release of MMP-9. We show that H. pylori LPS-elicited induction in gastric mucosal MMP-9 release is associated with MAPK, ERK and p38 activation, and occurs with the involvement of Rac1 and cytosolic phospholipase A2 (cPLA2). Further, we demonstrate that the LPS-induced MMP-9 release requires ERK-mediated phosphorylation of cPLA2 on Ser(505) that is essential for its membrane localization with Rac1, and that this process necessitates p38 participation. Moreover, we reveal that the activation and membrane translocation of p38 to the Rac1-GTP complex plays a pivotal role in cPLA2-dependent enhancement in MMP-9 release. Hence, our findings provide a strong evidence for the role of ERK/cPLA2 and Rac1/p38/cPLA2 cascade in H. pylori LPS-induced up-regulation in gastric mucosal MMP-9 release.
Insights
Helicobacter pylori infection triggers matrix metalloproteinase-9 (MMP-9) release in the gastric mucosa. This study reveals a Rac1/MAPK cascade involving ERK and p38 pathways that drives MMP-9 release.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cell Signaling
Background:
- Matrix metalloproteinases (MMPs), particularly MMP-9, are implicated in inflammatory diseases like H. pylori-associated gastritis and ulcers.
- H. pylori infection elevates MMP-9 production and activates mitogen-activated protein kinase (MAPK) and Rac1 signaling in gastric mucosa.
Purpose of the Study:
- To investigate the role of the Rac1/MAPK pathway in the release of MMP-9 induced by H. pylori lipopolysaccharide (LPS).
Main Methods:
- Investigated the involvement of MAPK (ERK, p38), Rac1, and cytosolic phospholipase A2 (cPLA2) in H. pylori LPS-induced MMP-9 release.
- Examined the phosphorylation and membrane localization of cPLA2 and the translocation of p38.
Main Results:
- H. pylori LPS induced MMP-9 release via MAPK, ERK, and p38 activation, involving Rac1 and cPLA2.
- ERK-mediated cPLA2 phosphorylation at Ser(505) was crucial for its membrane localization with Rac1, requiring p38.
- p38 activation and membrane translocation to the Rac1-GTP complex were vital for cPLA2-dependent MMP-9 release.
Conclusions:
- The ERK/cPLA2 and Rac1/p38/cPLA2 signaling cascades are critical for H. pylori LPS-induced upregulation of gastric mucosal MMP-9 release.
- This pathway provides a potential therapeutic target for H. pylori-associated gastric inflammation.
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