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Open Access 01-12-2017 | Research article

Helicobacter-induced gastric inflammation alters the properties of gastric tissue stem/progenitor cells

Authors: Wataru Shibata, Soichiro Sue, Sachiko Tsumura, Yasuaki Ishii, Takeshi Sato, Eri Kameta, Makoto Sugimori, Hiroaki Yamada, Hiroaki Kaneko, Tomohiko Sasaki, Tomohiro Ishii, Toshihide Tamura, Masaaki Kondo, Shin Maeda

Published in: BMC Gastroenterology | Issue 1/2017

Abstract

Background

Although Helicobacter-induced gastric inflammation is the major predisposing factor for gastric carcinogenesis, the precise mechanism by which chronic gastritis causes gastric cancer remains unclear. Intestinal and spasmolytic polypeptide-expressing metaplasia (SPEM) is considered as precancerous lesions, changes in epithelial tissue stem/progenitor cells after chronic inflammation has not been clarified yet. In this study, we utilized three-dimensional gastric epithelial cell culture systems that could form organoids, mimicking gastric epithelial layer, and characterized the changes in epithelial cells after chronic Helicobacter felis infection.

Methods

We used three mice model; 1) long-term H. felis infection, 2) H. felis eradication, and 3) MNU chemical carcinogenesis model. We performed cRNA microarray analysis after organoid culture, and analyzed the effects of chronic gastric inflammation on tissue stem cells, by the size of organoid, mRNA expression profile and immunohistochemical analysis.

Results

The number of organoids cultured from gastric epithelial cells was significantly higher in organoids isolated from H. felis-infected mice compared with those from uninfected gastric mucosa. Based on the mRNA expression profile, we found that possible stem cell markers such as Cd44, Dclk1, and genes associated with the intestinal phenotype, such as Villin, were increased in organoids isolated from H. felis-infected mucosa compared with the control. The upregulation of these genes were cancelled after H. felis eradication. In a xenograft model, tumors were generated only from organoids cultured from carcinogen-treated gastric mucosa, not from H. felis infected mucosa or control organoids.

Conclusions

Our results suggested that, as a possible mechanism of gastric carcinogenesis, chronic inflammation induced by H. felis infection increased the number of tissue stem/progenitor cells and the expression of stem cell markers. These findings suggest that chronic inflammation may alter the direction of differentiation toward undifferentiated state and that drawbacks may enable cells to redifferentiate to intestinal metaplasia or neoplasia.

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Title: Helicobacter-induced gastric inflammation alters the properties of gastric tissue stem/progenitor cells
Authors: Wataru Shibata
Soichiro Sue
Sachiko Tsumura
Yasuaki Ishii
Takeshi Sato
Eri Kameta
Makoto Sugimori
Hiroaki Yamada
Hiroaki Kaneko
Tomohiko Sasaki
Tomohiro Ishii
Toshihide Tamura
Masaaki Kondo
Shin Maeda
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Gastroenterology / Issue 1/2017
Electronic ISSN: 1471-230X
DOI: https://doi.org/10.1186/s12876-017-0706-6

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Helicobacter-induced gastric inflammation alters the properties of gastric tissue stem/progenitor cells

Abstract

Background

Methods

Results

Conclusions

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Abstract

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Conclusions

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