Involvement of Aquaporin 3 in Helicobacter pylori-related gastric diseases

PLoS One. 2012;7(11):e49104. doi: 10.1371/journal.pone.0049104. Epub 2012 Nov 9.

Abstract

Background: Gastric cancer is one of the most common and lethal malignant cancers worldwide, and numerous epidemiological studies have demonstrated that Helicobacter pylori (H. pylori) infection plays a key role in the development of gastric carcinomas. Our previous studies showed that aquaporin 3 (AQP3) is overexpressed in gastric carcinoma and promotes the migration and proliferation of human gastric carcinoma cells, suggesting that AQP3 may be a potentially important determinant of gastric carcinoma. However, the role of AQP3 in H. pylori carcinogenesis is unknown.

Methods: The AQP3 protein and H. pylori were detected in human gastric tissues by immunohistochemistry and modified Giemsa staining respectively. AQP3 knockdown was obtained by small interfering (si) RNA. Western blot assays and RT-PCR were used to evaluate the change of AQP3 in the human gastric cancer AGS and SGC7901 cell lines after co-culture with H. pylori. Sprague Dawley rats were orally inoculated with H. pylori to establish a rat model colonized by H. pylori.

Results: The present study found that AQP3 expression correlated with H. pylori infection status in gastric cancer tissues and corresponding normal mucosa, and H. pylori co-culture upregulated AQP3 expression in human gastric adenocarcinoma cells in vitro via the extracellular signal-regulated kinase signaling pathway. H. pylori infection also increased AQP3 expression in gastric mucosa colonized by H. pylori in a Sprague Dawley rat model.

Conclusions: These findings provide further information to understand the mechanism of H. pylori carcinogenesis and a potential strategy for the treatment of H. pylori-associated gastric carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Aquaporin 3 / genetics
  • Aquaporin 3 / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Helicobacter Infections / enzymology
  • Helicobacter Infections / metabolism*
  • Helicobacter Infections / microbiology*
  • Helicobacter Infections / pathology
  • Humans
  • Immunohistochemistry
  • MAP Kinase Signaling System
  • Male
  • Middle Aged
  • Rats
  • Rats, Sprague-Dawley
  • Stomach Diseases / enzymology
  • Stomach Diseases / metabolism*
  • Stomach Diseases / microbiology*
  • Stomach Diseases / pathology
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / pathology
  • Up-Regulation

Substances

  • AQP3 protein, human
  • Aqp3 protein, rat
  • Aquaporin 3
  • Extracellular Signal-Regulated MAP Kinases

Grants and funding

This work was funded by the Qing Lan Project, 7th “Six Talent-Person-Peak Program” of Jiangsu Province, and Key Medical Talent Program of Jiangsu Province. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.