Barrett食管（BE）发病的分子机理一直是研究热点。研究发现调控众多柱状上皮及鳞状上皮标志基因的Hedgehog（HH）通路异常激活,是BE发生及肠上皮化生的驱动者。靶向HH通路的抑制剂可能阻止BE进程。近期我们成功建立了BE organoids（类器官）培养系统用于探索影响BE进程，与HH通路相关的药物。我们发现：在BE organoids、BE细胞 及正常食管上皮细胞中，奥美拉唑可抑制HH通路转录因子Gli1、柱状上皮标志基因SOX9的转录及蛋白表达。据此我们设想奥美拉唑可能参与调控BE中HH通路并影响BE进程。本项目将以前期发现为基础，深入研究：①BE病程中奥美拉唑干预后的转录组学差异。② 在BE细胞、BE organoids、Swiss Webster鼠体内明确奥美拉唑对HH通路及其下游基因的影响。③探究奥美拉唑调控HH通路的具体分子机理。旨在揭示PPi的非抑酸途径新机制。

The mechanism that contributes to the progression of Barrett's esophagus (BE) has not been elucidated, nor the chemoprevention strategies for esophageal adenocarcinoma been recognized. Previous work implicated that hedgehog signaling was involved in the differentiation of squamous epithelium toward an intestinal-type columnar epithelium, suggested hedgehog signaling may be a possible driver of BE. And the potential inhibitors of the hedgehog pathway may be used in the treatment of BE. Recently, we have set up BE organoids for exploration of the pathogenesis of BE. Our date showed that omeprazole decreased the mRNA and expression of Gli1 and Sox9 in BE organoids, BE cells and normal esophagus epithelium cells. Thus, we hypothesized that omeprazole might possess acid-independent mechanism, and contribute to the modulation of hedgehog signaling in BE. To explore this hypothesis, we study the effects of Omeprazole on the regulation of hedgehog signaling in BE. Our aim is to further elucidate omeprazole's potential acid-independent mechanism in BE.