Molecular Mechanism of Gastric Carcinogenesis in Helicobacter pylori-Infected Rodent Models

Abstract

Since the discovery of Helicobacter pylori (H. pylori), many efforts have been made to establish animal models for the investigation of the pathological features and molecular mechanisms of gastric carcinogenesis. Among the animal models, Mongolian gerbils and mice are particularly useful for the analysis of H. pylori-associated inflammatory reactions and gastric cancer development. Inhibitors of oxidative stress, cyclooxygenase-2 (COX-2) and nuclear factor-κB, exert preventive effects on chronic gastritis and the development of adenocarcinomas in H. pylori-infected gerbils. Genetically-modified mouse models, including transgenic and knockout mice, have also revealed the importance of p53, COX-2/prostaglandin, Wnt/β-catenin, proinflammatory cytokines, gastrin and type III mucin in the molecular mechanisms of gastric carcinogenesis. Microarray technology is available for comprehensive gene analysis in the gastric mucosa of mouse models, and epigenetics, such as DNA methylation, could be an alternative approach to correlate the observations in animal models with the etiology in humans.

Trefoil factor 1 expression suppresses Helicobacter pylori–induced inflammation in gastric carcinogenesis

“…However, the reconstitution of TFF1 abolishes H. pylori -induced expression of these proinflammatory cytokines in gastric cancer cells. Several studies have demonstrated that the proinflammatory cytokines TNF α and IL1 β, known to be induced by NFκB 44 , are associated with gastric disease in rodents after H. pylori infection 45, 46 .…”

“…Several studies have demonstrated that the proinflammatory cytokines TNF-a and IL-1b, known to be induced by NF-jB, 45 are associated with gastric disease in rodents after H. pylori infection. 46,47 Long exposure to proinflammatory cytokines and sustained activation of signaling pathways such as NF-jB due to pathogen infection result in chronic inflammation, which promotes malignancy and tumorigenesis. 5,7,8 Accordingly, our data demonstrated that H. pylori infection of Tff1-KO mice led to significant increases in chronic inflammatory scores, the expression of proinflammatory cytokines, and the development of invasive gastric adenocarcinoma in comparison with uninfected Tff1-KO mice.…”

Establishment of an intragastric surgical model using C57BL/6 mice to study the vaccine efficacy of OMV-based immunogens againstHelicobacter pylori

“…Moreover, an efficient animal model is crucial to understanding the immunological attributes of different immunogen(s) for vaccine development, which existing models fail to satisfy. Considerable efforts have been made to establish a reliable murine (gerbil or mouse) model to serve this purpose, including extensive application of transgenic animals with single or double mutations, but unfortunately, no significant efforts have been made toward the route of administration to induce an infection [13]. The preexisting method relies on the oral administration of multiple doses of inoculums along with antibiotic pretreatment to induce an infection [14].…”