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Updated: Jul 2, 2026
Mouse- and Human-derived Primary Gastric Epithelial Monolayer Culture for the Study of Regeneration
Published on: May 7, 2018
Helicobacter pylori and mitogen-activated protein kinases regulate the cell cycle, proliferation and apoptosis in
Song-Ze Ding1, Michael F Smith, Joanna B Goldberg
1Department of Microbiology, The University of Virginia Health System, Charlottesville, Virginia 22908-0734, USA.
Background And Aims:
Helicobacter pylori infection activates mitogen-activated protein kinases (MAPK) and modulates cell proliferation and apoptosis. However, the relationship between H. pylori infection and MAPK signaling in controlling cell proliferation and apoptosis is not clear, nor has the role of MAPK on the gastric epithelial cell cycle and proliferation been established. Therefore, we investigated the effects of H. pylori infection and MAPK inhibition on these processes.
Methods:
Gastric epithelial cell lines (AGS and MKN45) were infected with H. pylori and/or treated with MAPK inhibitors. Cell cycle and apoptosis were measured by flow cytometry. Cell cycle proteins and proliferation were monitored by western blot and cell count, respectively.
Results:
Infection with H. pylori resulted in dose-dependent MAPK activation, cell cycle arrest, reduced proliferation and increased apoptosis. The effect of H. pylori and MAPK at various cell cycle checkpoints was noted: MEK1/2 and p38 inhibition increased H. pylori-induced cell cycle G(1) arrest, while JNK inhibition reduced G(1) arrest. MEK1/2 inhibition increased p21, p27 and cyclin E and JNK inhibition additionally increased cyclin D1 expression. Both inhibitors decreased cell proliferation. All inhibitors enhanced apoptosis after H. pylori infection. We also detected MAPK cross-talk in AGS cells: p38 and JNK inhibitors increased ERK activation. The p38 inhibitor increased JNK and the MEK1/2 inhibitor decreased JNK activation only during H. pylori infection.
Conclusions:
These results suggest H. pylori and MAPK differentially regulate the cell cycle, proliferation and apoptosis in gastric epithelial cells. The imbalance between H. pylori infection and MAPK activation likely contributes to the H. pylori-induced pathogenesis.
Insights
Helicobacter pylori infection impacts gastric cells by altering mitogen-activated protein kinases (MAPK) signaling, affecting cell cycle, proliferation, and apoptosis. Understanding this relationship is key to H. pylori pathogenesis.
Area of Science:
- Cell Biology
- Molecular Biology
- Gastroenterology
Background:
- Helicobacter pylori infection is known to activate mitogen-activated protein kinases (MAPK).
- The precise mechanisms by which MAPK signaling controls cell proliferation and apoptosis during H. pylori infection remain unclear.
- The role of MAPK in regulating the gastric epithelial cell cycle and proliferation requires further elucidation.
Purpose of the Study:
- To investigate the effects of H. pylori infection on MAPK signaling pathways.
- To determine how MAPK inhibition influences cell cycle progression, proliferation, and apoptosis in gastric epithelial cells.
- To elucidate the interplay between H. pylori and MAPK in gastric epithelial cell regulation.
Main Methods:
- Gastric epithelial cell lines (AGS and MKN45) were infected with H. pylori and treated with MAPK inhibitors (MEK1/2, p38, JNK).
- Cell cycle distribution and apoptosis were analyzed using flow cytometry.
- Expression of cell cycle regulatory proteins and cell proliferation rates were assessed via Western blot and cell counting.
Main Results:
- H. pylori infection induced dose-dependent MAPK activation, G1 cell cycle arrest, reduced proliferation, and increased apoptosis.
- MEK1/2 and p38 inhibition exacerbated H. pylori-induced G1 arrest, while JNK inhibition reduced it.
- MAPK inhibitors generally enhanced H. pylori-induced apoptosis and modulated cell cycle protein expression (p21, p27, cyclin E, cyclin D1).
- Evidence of MAPK cross-talk was observed, with inhibitors affecting the activation of other MAPK pathways.
Conclusions:
- H. pylori and MAPK signaling pathways differentially regulate cell cycle, proliferation, and apoptosis in gastric epithelial cells.
- The intricate balance between H. pylori infection and MAPK activation is crucial in the pathogenesis of H. pylori-related gastric diseases.
- Targeting MAPK pathways may offer therapeutic strategies for H. pylori-associated conditions.
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