胆汁酸、幽门螺旋杆菌等因素诱导尾型同源盒转录因子2表达致胃黏膜肠上皮化生研究进展

Research progress of CDX2 expression induced by bile acid,Helicobacter pylori and other factors in gastric intestinal metaplasia

胃黏膜肠上皮化生(GIM)是一种癌前病变,增加了后续胃癌(GC)发展的风险。因此,GIM一直是基础和临床研究的重点。尾型同源盒转录因子2(CDX2)是调节肠上皮细胞表型的肠特异性转录因子,主要存在于小肠和结肠,在正常胃黏膜中很少表达。幽门螺杆菌感染已被公认为GIM的主要致病因素,其通过核因子-kappaB信号通路及其下游的促炎因子、转化生长因子-β信号通路以及Sonic Hedgehog基因(Shh)来增加CDX2的表达,从而引起GIM。然而,越来越多的研究表明,胆汁反流引起的胃黏膜慢性炎症同样也是GIM的关键致病因素。胆汁反流通过其微小RNA、外泌体、表观遗传学及胆汁酸受体激活GIM生物标志物的表达导致GIM的发生和发展。目前,两大因素之外诱导CDX2的相关研究仍然很少。现对目前该领域的相关进展进行综述,为进一步研究提供参考。

Gastric intestinal metaplasia(GIM)is a precancerous lesion that increases the risk of subsequent gastric cancer(GC)development.Therefore,GIM has been the focus of basic and clinical research.Caudal type homebox 2(CDX2)is an enteric-specific transcription factor that regulates the phenotype of intestinal epithelial cells,which is mainly present in the small intestine and colon,and is rarely expressed in normal gastric mucosa.Helicobacter pylori infection has been recognized as the main pathogenic factor of GIM,which causes GIM by increasing the expression of CDX2 through the nuclear factor-kappaB signaling pathway and its downstream proinflammatory factors,transforming growth factor-βsignaling pathway and Sonic Hedgehog(Shh).However,more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is also a key pathogenic factor of GIM.Bile reflux leads to the occurrence and development of GIM through the expression of micro RNA,exosomes,epigenetics and bile acid receptor activated GIM biomarkers.At present,there are still few studies related to the induction of CDX2 beyond the two major factors.This article reviews the current progress in this field to provide reference for further research.