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Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation
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 STAT...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911338/ https://www.ncbi.nlm.nih.gov/pubmed/29849601 http://dx.doi.org/10.1155/2018/9050715 |
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author | 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 |
author_facet | 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 |
author_sort | Ishii, Yasuaki |
collection | PubMed |
description | 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 (Stat3(Δgec)) 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 Stat3(Δgec) 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. |
format | Online Article Text |
id | pubmed-5911338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-59113382018-05-30 Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation 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 Gastroenterol Res Pract Research Article 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 (Stat3(Δgec)) 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 Stat3(Δgec) 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. Hindawi 2018-04-08 /pmc/articles/PMC5911338/ /pubmed/29849601 http://dx.doi.org/10.1155/2018/9050715 Text en Copyright © 2018 Yasuaki Ishii et al. http://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Research Article 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 Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation |
title | Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation |
title_full | Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation |
title_fullStr | Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation |
title_full_unstemmed | Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation |
title_short | Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes to Helicobacter-Associated Gastric Epithelial Proliferation and Inflammation |
title_sort | activation of signal transduction and activator of transcription 3 signaling contributes to helicobacter-associated gastric epithelial proliferation and inflammation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911338/ https://www.ncbi.nlm.nih.gov/pubmed/29849601 http://dx.doi.org/10.1155/2018/9050715 |
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