Traulsen Jan, Zagami Claudia, Daddi Alice Anna, Boccellato Francesco
Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, United Kingdom.
Best Pract Res Clin Gastroenterol. 2021 Mar-Apr;50-51:101737. doi: 10.1016/j.bpg.2021.101737. Epub 2021 Feb 22.
The lining of the stomach is a tight monolayer of epithelial cells performing functions in digestion and a protective barrier against gastric acid, toxic metabolites and infectious agents, including Helicobacter pylori. The response of the epithelial barrier to infections underlies gastric pathologies, including gastric cancer. H. pylori has the unique capacity to colonise the gastric mucosa while evading the immune system. The colonised mucosa initiates an inflammatory response to fight the infection and a strong regenerative program to avoid barrier failure and ulceration. This response changes the morphology and cell composition of the gastric epithelium and in parallel it might contribute to the accumulation of somatic mutations leading to cellular transformation. Genetically modified mice, cell lines and human-derived organoids are the main biological models to study the gastric epithelial barrier. With these models it is possible to dissect the stepwise process of tissue adaptation to infection that places the epithelium at risk of malignant transformation.
胃黏膜是一层紧密排列的上皮细胞单层，在消化过程中发挥作用，并作为抵御胃酸、有毒代谢产物和包括幽门螺杆菌在内的感染因子的保护屏障。上皮屏障对感染的反应是包括胃癌在内的胃部疾病的基础。幽门螺杆菌具有在逃避免疫系统的同时定植于胃黏膜的独特能力。被定植的黏膜引发炎症反应以对抗感染，并启动强大的再生程序以避免屏障功能衰竭和溃疡形成。这种反应改变了胃上皮的形态和细胞组成，同时可能导致体细胞突变的积累，从而引发细胞转化。基因编辑小鼠、细胞系和人源类器官是研究胃上皮屏障的主要生物学模型。利用这些模型，可以剖析组织对感染的逐步适应过程，而这一过程使上皮细胞面临恶性转化的风险。
