Cytotoxin-associated-gene A (CagA) of Helicobacter pylori (H. pylori) is a virulence factor that plays critical roles in H. pylori-induced gastric inflammation. In the present study, gastric biopsies were used for genotyping cagA and vacA genes, determining the autophagic activity, and the severity of gastric inflammation response. It was revealed that autophagy in gastric mucosal tissues infected with cagA+ H. pylori strains was lower than the levels produced by cagA− H. pylori strains, accompanied with accumulation of SQSTM1 and decreased LAMP1 expression. In vitro, deletion mutant of cagA gene resulted in increased autophagic activity, and decreased expression of SQSTM1 and cytokines, whereas over-expression of CagA down-regulated the starvation-induced autophagy, and induced more production of the cytokines. Moreover, the production of the cytokines was increased by inhibition of autophagy, but decreased by enhancement of autophagy. Deletion of CagA decreased the ability to activate Akt kinase at Ser-473 site and increased autophagy. c-Met siRNA significantly affected CagA-mediated autophagy, and decreased the level of p-Akt, p-mTOR, and p-S6. Both c-Met siRNA and MK-2206 could reverse inflammatory response. H. pylori CagA protein negatively regulates autophagy and promotes the inflammation in H. pylori infection, which is regulated by c-Met-PI3K/Akt-mTOR signaling pathway activation.

Background: Increasing evidence has shown that Helicobacter pylori is associated with coronary heart disease (CHD); however, the underlying mechanism remains unclear.Methods: The expression of miR-25 and mRNAs was measured using qRT-PCR. Protein levels were detected using western blotting and exosomes were assessed with an electron microscope. The target gene of miR-25 was identified using the luciferase report system.Results: H. pylori infection increased the expression of miR-25 in gastric epithelial cells and was associated with increased levels of exosome-transmitted miR-25 in human peripheral blood. Mechanistic investigation showed the Kruppel-like factor 2 (KLF2) was a direct target of exosome-transmitted miR-25 in vascular endothelial cells. In addition, the miR-25/KLF2 axis regulated the NF-κB signaling pathway, resulting in increased expression of interleukin 6 (IL6), monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1).Conclusion: Our findings suggest that the miR-25/KLF2 axis may be a potential therapeutic target for H. pylori-associated CHD. Furthermore, high levels of exosome-transmitted miR-25 in peripheral blood may pose a potential risk for CHD.

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Key indicatorsSingle-crystal X-ray study T = 293 K Mean (C-C) = 0.006 Å R factor = 0.062 wR factor = 0.126 Data-to-parameter ratio = 8.6For details of how these key indicators were automatically derived from the article, see