幽门螺杆菌CagA蛋白及其致病机制的研究进展

幽门螺杆菌感染是导致从胃炎到胃癌等一系列胃相关疾病的主要病因,但具体的致病机制仍不是很清楚。细胞毒素相关蛋白A(cytotoxin-associated gene A,Cag A)是幽门螺杆菌编码的一种重要毒力因子,且作为细菌来源的唯一癌蛋白被大量研究。Cag A蛋白是由幽门螺杆菌Ⅳ型分泌系统介导并注入宿主胃上皮细胞内,一旦进入细胞,Cag A能够与多个分子发生相互作用,扰乱细胞正常的信号通路,引起细胞病变和转化,而动物实验也证明了Cag A蛋白的致癌特点。本文重点对Cag A蛋白的序列特征,转位方式及致病机制等方面的最新进展进行了综述,希望能进一步阐释Cag A介导的幽门螺杆菌的致病机制,为以后的研究提供一定的方向和指导。

Advances in CagA protein and CagAmediated pathogenesis of Helicobacter pylori-A review

Helicobacter pylori (H. pylori) is a strong risk factor for gastric disease ranging from chronic gastritis to gastric cancer. But the mechanisms underlying the pathogenesis of H. pylori are still not completely understood.The cytotoxin-associated gene A (CagA) of H. pylori, an important virulence factor and the only bacterial oncoprotein, is extensively studied. CagA is delivered into gastric epithelial cells via type IV secretion of H. pylori. Upon delivery, CagA perturbs multiple host signaling pathways by interacting with the host signaling molecules, resulting in cytopathic effects and subsequent cell transformation. Some animal experiments also provide in vivo evidence for the oncogenic capacity of CagA. In this review, recent advances in the structural property, delivery manner and pathogenesis of CagA are summarized, which we hope could better explain the CagA-mediated pathogenesis of Helicobacter pylori and provide directions for the future approach.