Hypoxia exacerbates the malignant transformation of gastric epithelial cells induced by long-term H. pylori infection

• DOI: 10.1128/spectrum.00311-24
• Publication Date: 2024-06-25T13:01:32Z
• Authors: Yang He; Xiulin Zhang; Xiaolu Zhang; Bo Fu; Jin Xing; Rui Fu; Jianyi Lv; Meng Guo; Xueyun Huo; Xin Liu; Jing Lu; Lixue Cao; Xiaoyan Du; Zhongming Ge; Zhenwen Chen; Xuancheng Lu; Changlong Li
• Keywords: Hypoxia; Malignant Transformation

ABSTRACT Helicobacter pylori is a microaerophilic Gram-negative bacterium that resides in the human stomach and classified as class I carcinogen for gastric cancer. Numerous studies have demonstrated H. infection plays role regulating function of host cells, thereby contributing to malignant transformation these cells. However, chronic process, short-term cellular experiments may not provide comprehensive understanding vivo situation, especially when considering lower oxygen levels stomach. In this study, we aimed investigate mechanisms underlying cell dysfunction after prolonged exposure under hypoxic conditions. We conducted co-culture experiment using line GES-1 30 generations intermittent By closely monitoring proliferation, migration, invasion, autophagy, apoptosis, revealed sustained stimulation conditions significantly influences This induces epithelial-mesenchymal transition contributes propensity To confirm vitro results, an involving Mongolian gerbils infected with 85 weeks. All results strongly suggest Nod1 receptor signaling pathway crucial -related apoptosis autophagy. summary, continuous by affects functioning cells through pathway, increasing likelihood carcinogenesis. The presence further exacerbates process. IMPORTANCE Deciphering collaborative effects on epithelial key unraveling development Prior research has solely examined outcomes aerobic conditions, neglecting bacterium’s nature organism leads cancer following colonization. study mimics more genuine scenario repeatedly exposing up generations. show hypoxia substantially increases transition, while suppressing autophagy apoptosis. highlights significance intensifying carcinogenic impact infection. accurately replicating environment, enhances our comprehension ’s pathogenic