Hedgehog信号通路在Barrett食管发病机制中的研究进展

Advances in Study on Hedgehog Signaling Pathway in Pathogenesis of Barrett's Esophagus

Hedgehog(Hh)信号通路在脊椎动物体内具有高度进化保守性,其过度活化可引起细胞分化异常、过度增殖、抗凋亡以及促进肿瘤细胞侵袭和转移。Hh通路参与维持正常早期胚胎食管柱状上皮的形成,而在成体食管鳞状上皮中不表达或微弱表达。有研究证实胃酸和胆汁酸盐可激活食管上皮Hh通路。异常激活的Hh通路可引起正常食管鳞状上皮逐步转化为柱状上皮和肠上皮,并最终诱导Barrett食管(BE)形成。因此,靶向作用于Hh通路的抑制剂有望成为治疗BE的新策略。本文就Hh信号通路在BE发病机制中的研究进展作一综述。

Hedgehog （Hh） signaling pathway is evolutionarily conserved in vertebrates, its excessive activation is associated with abnormal cell differentiation, over proliferation, apoptosis resistance and promotion of invasion and metastasis of tumor cells. Hh signaling pathway involves in the formation and maintenance of esophageal columnar epithelium in embryonic stage, however, undetectable or barely expressed in matured esophageal squamous epithelium. Studies have shown that esophageal Hh signaling pathway can be activated by gastric acid and bile salts. Aberrant activation of Hh signaling pathway can cause the gradual transition of squamous epithelium to columnar epithelium and intestinal-type epithelium, ultimately induces the occurrence of Barrett＇ s esophagus （BE）. Therefore, targeted inhibiting the Hh signaling pathway may be a new strategy for the treatment of BE. This article reviewed the advances in study on Hh signaling pathway in the pathogenesis of BE.