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- Title
Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation.
- Authors
Ishii, Yasuaki; Shibata, Wataru; Sugimori, Makoto; Kaneta, Yoshihiro; Kanno, Masatomo; Sato, Takeshi; Sue, Soichiro; Kameta, Eri; Kaneko, Hiroaki; Irie, Kuniyasu; Sasaki, Tomohiko; Kondo, Masaaki; Maeda, Shin
- Abstract
<italic>Background/Aim</italic>. Although IL-6-mediated activation of the signal transduction and activator of transcription 3 (STAT3) axis is involved in inflammation and cancer, the role of STAT3 in <italic>Helicobacter</italic>-associated gastric inflammation and carcinogenesis is unclear. This study investigated the role of STAT3 in gastric inflammation and carcinogenesis and examined the molecular mechanism of <italic>Helicobacter</italic>-induced gastric phenotypes. <italic>Methods</italic>. To evaluate the contribution of STAT3 to gastric inflammation and carcinogenesis, we used wild-type (WT) and gastric epithelial conditional <italic>Stat3</italic>-knockout (<italic>Stat3Δgec</italic>) mice. Mice were infected with <italic>Helicobacter felis</italic> and euthanized at 18 months postinfection. Mouse gastric organoids were treated with recombinant IL-6 (rIL-6) or rIL-11 and a JAK inhibitor (JAKi) to assess the role of IL-6/STAT3 signaling <italic>in vitro</italic>. <italic>Results</italic>. Inflammation and mucous metaplasia were more severe in WT mice than in <italic>Stat3Δgec</italic> mice. The epithelial cell proliferation rate and STAT3 activation were increased in WT mice. Application of rIL-6 and rIL-11 induced expression of intestinal metaplasia-associated genes, such as <italic>Tff2</italic>; this induction was suppressed by JAKi administration. <italic>Conclusions</italic>. Loss of STAT3 signaling in the gastric mucosa leads to decreased epithelial cell proliferation, atrophy, and metaplasia in the setting of <italic>Helicobacter</italic> infection. Therefore, activation of STAT3 signaling may play a key role in <italic>Helicobacter</italic>-associated gastric carcinogenesis.
- Subjects
HELICOBACTER diseases; CARCINOGENESIS; PHENOTYPES; METAPLASIA; JAK-STAT pathway
- Publication
Gastroenterology Research & Practice, 2018, p1
- ISSN
1687-6121
- Publication type
Article
- DOI
10.1155/2018/9050715