Activation of Aquaporin 5 by carcinogenic Helicobacter pylori infection promotes epithelial‐mesenchymal transition via the MEK/ERK pathway

Nianshuang Li; Xinbo Xu; Hui Yang; Huan Wang; Yaobin Ouyang; Yanan Zhou; Chao Peng; Zhenxiang Yuan; Cong He; Chunyan Zeng; Junbo Hong

doi:10.1111/hel.12842

journal article Jul 30, 2021

Activation of Aquaporin 5 by carcinogenic Helicobacter pylori infection promotes epithelial‐mesenchymal transition via the MEK/ERK pathway

Nianshuang Li Xinbo Xu

Hui Yang

Huan Wang

Yaobin Ouyang Yanan Zhou

Chao Peng

Zhenxiang Yuan Cong He Chunyan Zeng

Junbo Hong

Helicobacter Vol. 26 No. 5 · Wiley

View at Publisher Save 10.1111/hel.12842

Abstract

AbstractBackgroundHelicobacter pylori (H. pylori) is a major risk factor for gastric cancer. The water channel protein Aquaporin 5 (AQP5) is involved in the tumorigenesis and progression of various cancers. In this study, we aimed to explore the role of AQP5 in H. pylori‐induced gastric carcinogenesis.Materials and MethodsWe collected 160 samples which inculded CNAG, IM, Dys and gastric cancer from patients who underwent endoscopy and detected the expression of AQP5. In vivo and vitro H. pylori infection models, we explored the relationship between AQP5 and H. pylori. Plasmid, siRNA and inhibitors were used to investigated the relationship between AQP5 and EMT and the role of AQP5 in H. pylori‐induced gastric carcinogenesis.ResultAQP5 expression was gradually increased in human gastric tissues with the progression of chronic nonatrophic gastritis to gastric cancer and associated with the H. pylori infection status. In vivo and in vitro studies showed that H. pylori infection induced AQP5 expression in gastric epithelial cells in a CagA‐dependent manner. Knockdown of AQP5 reversed H. pylori‐induced cell proliferation and invasion, and ‐suppressed cell apoptosis. Additionally, knockdown of AQP5 suppressed H. pylori‐induced Epithelial‐mesenchymal transition (EMT) phenotypes by regulating transcriptional factors, mesenchymal markers, and epithelial markers.ConclusionsWe explored the underlying mechanism and our results indicated that knockdown of AQP5 significantly suppressed H. pylori infection‐induced phosphorylation of ERK1/2, MEK and the expression levels of downstream genes. Treatment with an ERK inhibitor suppressed the EMT induced by H. pylori infection. Taken together, this study suggest that pathogenic H. pylori infection promotes AQP5 expression to induce the EMT via the MEK/ERK signaling pathway.

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Details

Published: Jul 30, 2021
Vol/Issue: 26(5)
License: View

Authors

N

Nianshuang Li

Department of Gastroenterology The First Affiliated Hospital of Nanchang University Nanchang China; Institute of Digestive Disease The First Affiliated Hospital of Nanchang University Nanchang China

X

Xinbo Xu