title: Gastric Metaplasia Induced by Helicobacter pylori Is Associated with Enhanced SOX9 Expression via Interleukin-1 Signaling.
abstract: Histopathological changes of the gastric mucosa after Helicobacter pylori infection, such as atrophy, metaplasia, and dysplasia, are considered to be precursors of gastric cancer, yet the mechanisms of histological progression are unknown. The aim of this study was to analyze the histopathological features of the gastric mucosa in mice infected with H. pylori strain PMSS1 in relation to gastric stem cell marker expression. C57BL/6J mice infected with PMSS1 were examined for histopathological changes, levels of proinflammatory cytokines, and expression of stem cell markers. Histopathological gastritis scores, such as atrophy and metaplasia, and levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), were increased after PMSS1 infection. Expression levels of the cell proliferation and stem cell markers CD44 and SOX9 were also significantly increased in PMSS1-infected mice. Importantly, almost all metaplastic cells induced by PMSS1 infection expressed SOX9. When IL-1 receptor (IL-1R) knockout mice were infected with PMSS1, metaplastic changes and expression levels of stem cell markers were significantly decreased compared with those in wild-type (WT) mice. In conclusion, H. pylori infection induced the expression of cytokines and stem cell markers and histopathological metaplasia in the mouse gastric mucosa. SOX9 expression, in particular, was strongly associated with metaplastic changes, and these changes were dependent on IL-1 signaling. The results suggested the importance of SOX9 in gastric carcinogenesis.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Serizawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan hiratay-int@h.u-tokyo.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoku
authors.initials: Y
authors.lastname: Hayakawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Nobumi
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Division of Gastroenterology, Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Sakitani
authors.affiliation: Division of Gastroenterology, Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan.
authors.forename: Yohko
authors.initials: Y
authors.lastname: Hikiba
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Sozaburo
authors.initials: S
authors.lastname: Ihara
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kinoshita
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tateishi
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology* / Q000648:ultrastructure; D005756:Gastritis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000276:immunology / Q000472:pathogenicity*; D018960:Hyaluronan Receptors / Q000235:genetics; D007375:Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008679:Metaplasia / Q000382:microbiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055758:SOX9 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D018960:Hyaluronan Receptors; D007375:Interleukin-1; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse