Zuo Wei, Yang Hui, Li Nianshuang, Ouyang Yaobin, Xu Xinbo, Hong Junbo
Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, P. R. China.
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, P. R. China.
Cell Death Discov. 2022 May 10;8(1):257. doi: 10.1038/s41420-022-01026-0.
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.
幽门螺杆菌（H. pylori）感染是公认的胃炎致病因素，但其潜在机制仍有待确定。有趣的是，根据与幽门螺杆菌感染相关的微阵列数据预测，水通道蛋白5（AQP5）在肠化生（IM）中高表达，并且通过生物信息学预测转录因子无调性家族蛋白1（ASCL1）与AQP5相关。因此，本研究的目的是评估ASCL1和AQP5在幽门螺杆菌感染性胃炎中的机制意义。通过幽门螺杆菌感染建立胃炎小鼠模型，随后测定胃黏膜中AQP5和ASCL1的水平。此外，使用AQP5基因敲除小鼠探讨AQP5对幽门螺杆菌诱导的胃炎的影响。观察到幽门螺杆菌感染可提高胃黏膜和胃上皮细胞（GECs）中AQP5和ASCL1的表达。幽门螺杆菌通过调节ASCL1诱导AQP5表达，并激活GECs中的WNT/β-连环蛋白信号通路。还发现敲低AQP5可抑制幽门螺杆菌感染小鼠的炎症反应和细胞凋亡。此外，幽门螺杆菌感染导致的ASCL1和AQP5表达升高促进了GECs的细胞凋亡和炎症。综上所述，本研究的关键发现表明，幽门螺杆菌感染通过上调ASCL1/AQP5激活WNT/β-连环蛋白信号通路，从而诱发胃炎。
