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Gastroenterology Research and Practice
Volume 2018, Article ID 9050715, 9 pages
https://doi.org/10.1155/2018/9050715
Research Article

Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation

1Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
2Advanced Medical Research Center, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan

Correspondence should be addressed to Shin Maeda; pj.ca.uc-amahokoy@adeams

Received 23 September 2017; Revised 25 December 2017; Accepted 14 January 2018; Published 8 April 2018

Academic Editor: Haruhiko Sugimura

Copyright © 2018 Yasuaki Ishii et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aim. 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 Helicobacter-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 Helicobacter-induced gastric phenotypes. Methods. To evaluate the contribution of STAT3 to gastric inflammation and carcinogenesis, we used wild-type (WT) and gastric epithelial conditional Stat3-knockout (Stat3Δgec) mice. Mice were infected with Helicobacter felis 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 in vitro. Results. Inflammation and mucous metaplasia were more severe in WT mice than in Stat3Δgec 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 Tff2; this induction was suppressed by JAKi administration. Conclusions. Loss of STAT3 signaling in the gastric mucosa leads to decreased epithelial cell proliferation, atrophy, and metaplasia in the setting of Helicobacter infection. Therefore, activation of STAT3 signaling may play a key role in Helicobacter-associated gastric carcinogenesis.