Helicobacter pylori infection activates Wnt/β-catenin pathway to promote the occurrence of gastritis by upregulating ASCL1 and AQP5

Abstract

Helicobacter pylori (H. pylori) infection is a well-recognized contributing factor to gastritis, but the underlying mechanisms remain to be established. It is interesting to note that AQP5 was predicted to be highly expressed in intestinal metaplasia (IM) based on H. pylori infection-related microarray data, and the transcription factor ASCL1 was bioinformatically predicted to associate with AQP5. Therefore, the purpose of this study is to evaluate the mechanistic significance of ASCL1 and AQP5 in H. pylori infection of gastritis. Gastritis mouse models were established by H. pylori infection, followed by determination of AQP5 and ASCL1 in gastric mucosa. Besides, the effects of AQP5 on H. pylori-induced gastritis were explored using AQP5−/− mice. It was observed that H. pylori infection elevated expression of AQP5 and ASCL1 in gastric mucosa and gastric epithelial cells (GECs). H. pylori induced AQP5 expression by regulating ASCL1 and activated WNT/β-catenin signaling pathway in GECs. It was also found that AQP5 knockdown suppressed inflammatory response and apoptosis in H. pylori-infected mice. Moreover, H. pylori infection-elevated ASCL1 and AQP5 expression promoted apoptosis and inflammation in GECs. Taken together, the key findings of the present study demonstrate that H. pylori infection activated WNT/β-catenin signaling pathway by upregulating ASCL1/AQP5 to induce gastritis.