1. Targeting Host Sulphonyl Urea Receptor 2 Can Reduce Severity of Helicobacter pylori Associated Gastritis.
- Author
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Sarkar S, Alipour Talesh G, Menheniott TR, and Sutton P
- Abstract
Background and Aims: While most Helicobacter pylori -infected individuals remain asymptomatic throughout their lifetime, in a significant proportion, the resulting severe chronic gastritis drives the development of gastric cancer. In this study, we examine a new therapeutic target, a host potassium channel regulatory subunit, SUR2 (encoded by ABCC9 ), with potential to protect against H pylori -associated diseases., Methods: SUR2 gene (ABCC9) expression in human gastric biopsies was analyzed by quantitative polymerase chain reactions. Helicobacter- infected mice were administered the SUR2-channel agonists, pinacidil and nicorandil, then gastric tissues analyzed by histology, immunohistochemistry and quantitative polymerase chain reaction, and splenic tissues by enzyme-linked immunosorbent assays. In vitro studies were performed on human and mouse macrophages, human gastric epithelial cells and mouse splenocytes., Results: ABCC9 expression in human and mouse stomachs is downregulated with H pylori infection. Treatment of Helicobacter -infected mice with SUR2 channel modulators, pinacidil or nicorandil, significantly reduced gastritis severity. In gastric epithelial cells, nicorandil-induced opening of the SUR2 channel increased intracellular K
+ and prevented H pylori -mediated Ca2+ influx and downstream pro-inflammatory signaling., Conclusion: SUR2 is a novel host factor that regulates Helicobacter pathogenesis. Pharmacological targeting of SUR2 provides a potential approach for reducing the severity of H pylori -associated gastritis, without eradicating infection., (© 2023 The Authors.)- Published
- 2023
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