Work

Biphasic Adaptations of Gastric Epithelial Cells in Chronic H. pylori Infection from Stress to Tolerance

Year: 2025

Type: article

Abstract: Helicobacter pylori (H. pylori) is a well-known pathogen associated with chronic gastric infection, progressing from gastritis to gastric adenocarcinoma, but the dynamic phenotypic and molecular characteristics of gastric epithelial cells during sustained infection remain unclear. We established a chronic infection model using the human gastric epithelial cell line GES-1, exposed to H. pylori or its lysate across 30 generations, dynamically assessing cell proliferation, migration, invasion, apoptosis, autophagy, and epithelial–mesenchymal transition (EMT) markers, with RNA sequencing for transcriptomic changes and a Mongolian gerbil model to validate chronic pathological progression. Acute H. pylori exposure induced pronounced morphological changes; suppressed proliferation, migration, and invasion; triggered apoptosis; and blocked autophagic flux, while long-term stimulation reversed these effects. EMT markers showed progressive loss of epithelial characteristics with chronic infection. RNA sequencing revealed a dynamic shift from inflammation-driven apoptosis to adaptive survival mechanisms. In vivo, prolonged infection induced dynamic TLR expression alongside progressive gastric pathology, including atrophy and dysplasia. Our study provides new molecular evidence for dynamic cellular and immunological adaptations of gastric epithelial cells under chronic H. pylori infection, highlighting critical intervention windows for preventing gastric carcinogenesis.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26189016