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

Gastroenterology Research and Practice
Yasuaki IshiiShin Maeda

Abstract

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. 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. 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. Loss of STAT3 signaling in the gastric mucosa leads to decreased epithelial cell pro...Continue Reading

References

Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·K TakedaS Akira
Sep 15, 2001·The New England Journal of Medicine·N UemuraR J Schlemper
Aug 10, 2004·Gastroenterology·Sachiyo NomuraJames R Goldenring
Feb 1, 2005·Developmental Biology·Catherine S LeeKlaus H Kaestner
Jun 20, 2007·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Shoichiro Tsugane, Shizuka Sasazuki
Aug 8, 2007·Gastroenterology·Pelayo Correa, Jeanmarie Houghton
Apr 24, 2008·The Journal of Clinical Investigation·Matthias ErnstBrendan J Jenkins
Feb 3, 2009·Cancer Cell·Jacqueline Bromberg, Timothy C Wang
Apr 7, 2009·Methods in Molecular Biology·Arlin B Rogers, JeanMarie Houghton
May 6, 2009·Stem Cells·Shigeo TakaishiTimothy C Wang
Oct 13, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shin MaedaMasao Omata
Nov 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yumiko FujiiMasanori Hatakeyama
Dec 24, 2013·Cancer Research·Toru AtsumiMasaaki Murakami
Jul 26, 2014·Journal of Gastric Cancer·Sungsook YuKi Taek Nam
Aug 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Tomomi TadokoroBrigid L M Hogan
Jan 8, 2016·Digestive Diseases and Sciences·Shin HamadaTooru Shimosegawa
Aug 9, 2016·Cell Reports·Abby SarkarKonrad Hochedlinger
Dec 9, 2016·British Journal of Cancer·Hirokazu KodamaMasaji Tani
Feb 9, 2017·Cellular and Molecular Gastroenterology and Hepatology·Christine P PetersenJames R Goldenring

❮ Previous
Next ❯

Citations

Sep 6, 2019·Helicobacter·Armelle Ménard, Annemieke Smet
Mar 24, 2020·The American Journal of Pathology·Jesse J BalicBrendan J Jenkins
Apr 15, 2021·Brazilian Journal of Microbiology : [publication of the Brazilian Society for Microbiology]·Malak ZoaiterZaher Zeaiter

❮ Previous
Next ❯

Methods Mentioned

BETA
Infection
PCR
electrophoresis

Related Concepts

Related Feeds

Atrophic Gastritis

Atrophic Gastritis is a process where gastric glandular cells are lost and replaced with firbous tissues, as a result of chronic inflammation. Learn more about Atrophic Gastritis here.