Autophagy-driven modulation of stem cell dynamics in Helicobacter pylori -induced gastric diseases in mice

作者：Jing Li, Sisi Liu, Zhiqin Li, Chunlei Ma, Boqing Li, Yingzi Cui, W. Wang, Huilin Zhao, Xiaofei Ji, Ying Zhang · 发表于：Virulence · 年份：2025 · DOI：10.1080/21505594.2025.2551176 · 被引用次数：4 · 研究领域：Helicobacter pylori-related gastroenterology studies、Autophagy in Disease and Therapy、MicroRNA in disease regulation

Chronic Helicobacter pylori infection is a major contributor to gastric disease progression, with its involvement in autophagy and stem cell dynamics playing a critical role in disease mechanisms. This study investigated how H. pylori, particularly in combination with the carcinogen N-nitroso-N-methylurea (NMU), disrupted autophagy and stem cell function, driving gastric pathology. H. pylori infection significantly increased autophagy, promoted the epithelial–mesenchymal transition, suppressed Tff2 and Ghrelin expression in mouse gastric organoids, and enhanced stem cell proliferation (organoid numbers increased 92% compared to control at 24 weeks, p < 0.001), while NMU caused milder autophagy, severe inflammation, glandular dilation, and reduced stemness markers (CD133 decreased 30% at 24 weeks, p < 0.05). Combined H. pylori and NMU exposure synergistically dysregulated Tff2/Ghrelin expression, exacerbated autophagic flux disruption, and impaired stem cell function, reducing organoid budding (decreased 43% vs. H. pylori alone at 36 weeks, p < 0.01) and dysregulating CD133, CD44, Lgr5, and SOX2 expression. Pathologically, this combination led to severe gastric damage, including intestinal metaplasia and neutrophil infiltration. Chloroquine (CQ) treatment mitigates these effects by reversing autophagic dysfunction, restoring stem cell capacity (Lgr5 increased 97% at 44 weeks, p < 0.05), differentially modulating Tff2/Ghrelin: potentiating Tff2 and suppressing Ghrelin, normaliz...