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

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

  • Int J Mol Sci. 2025 Sep 16;26(18):9016. doi: 10.3390/ijms26189016.
Xiulin Zhang 1,  Yang He 2,  Xiaolu Zhang 1 3,  Ziyi Liang 1,  Wendong Wang 1,  Zhenyu Da 1,  Jianyi Lv 1,  Meng Guo 1,  Xueyun Huo 1,  Xin Liu 1,  Jing Lu 1,  Lixue Cao 1,  Xiaoyan Du 1,  Zhongming Ge 4,  Zhenwen Chen 1,  Xuancheng Lu 5,  Jianzhong Zhang 6,  Changlong Li 1
Affiliations

Affiliations

  • 1 Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Medical Genetics and Developmental Biology, School of Basic Medical Science, Capital Medical University, Beijing 100069, China.
  • 2 School of Nursing, Dalian Medical University, Dalian 116044, China.
  • 3 Department of Molecular Cell Biology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
  • 4 Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 5 National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Chinese Center for Disease Control and Prevention (Chinese Academy of Preventive Medicine), Beijing 102206, China.
  • 6 National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention (Chinese Academy of Preventive Medicine), Beijing 102206, China.
PMID: 41009587 DOI: 10.3390/ijms26189016
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.

Keywords

Helicobacter pylori; chronic infection; gastric epithelial cells.

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