Notch Signaling Pathway Is Inhibited in the Development of Barrett's Esophagus: An In Vivo and In Vitro Study.

Notch Signaling Pathway Is Inhibited in the Development of Barrett's Esophagus: An In Vivo and In Vitro Study.
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Notch 信号通路在 Barrett 食管的发育中受到抑制:一项体内和体外研究

DOI:
10.1155/2018/4149317
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发表时间:
2018
影响因子:
2.7
通讯作者:
Chen LQ
Chen LQ
中科院分区:
医学4区
文献类型:
--
作者:
Wang YC;Wang ZQ;Yuan Y;Ren T;Ni PZ;Chen LQ

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目的探讨Notch信号在Barrett食管发生发展中的作用。方法选择食管癌切除加胃间置术患者作为胃食管反流病的人类模型。采用真实的实时定量聚合酶链反应(RT-qPCR)和免疫组化(IHC)方法检测Notch信号基因在正常食管组织和食管癌术后残端柱状化生组织中的表达。在体外实验中,用盐酸、脱氧胆酸、盐酸和脱氧胆酸的混合物或Notch 1-siRNA处理Het-1A细胞,并通过RT-qPCR和western blot评估Notch 1、Hes 1、MUC 2和K13的表达。结果36例食管残端柱状上皮化生患者的标本均经病理证实。免疫组化和RT-qPCR均显示Notch 1和Hes 1在正常食管组织中的表达明显高于食管上皮化生组织。盐酸和脱氧胆酸抑制Notch 1、Hes 1和K13的表达,同时增加MUC 2的表达。Notch 1-siRNA抑制Notch导致Notch 1、Hes 1和K13表达下调,而MUC 2表达增强。结论盐酸和脱氧胆酸均可抑制食管上皮细胞Notch信号通路,抑制Notch信号通路在Barrett食管的发生发展中具有重要作用。
Objective To explore the role of Notch signaling in the development of Barrett's esophagus. Methods Patients with esophagectomy and gastric interposition were recruited as a human model of gastroesophageal reflux disease. The expressions of Notch signaling genes in normal esophagus from surgical specimen and columnar metaplasia in the esophageal remnant after esophagectomy were evaluated by real time quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry (IHC). For in vitro experiments, Het-1A cells were treated with hydrochloric acid, deoxycholic acid, mixture of hydrochloric acid and deoxycholic acid, or Notch1-siRNA, and expressions of Notch1, Hes1, MUC2, and K13 were evaluated via RT-qPCR and western blot. Results Samples were obtained from 36 patients with columnar metaplasia in the esophageal remnant. Both IHC and RT-qPCR indicated that Notch1 and Hes1 expressions were significantly higher in normal esophagus than that in metaplasia. Hydrochloric acid and deoxycholic acid suppressed Notch1, Hes1, and K13 expressions, in concert with increasing MUC2 expressions. Notch inhibition by Notch1-siRNA contributed to the downregulation of Notch1, Hes1, and K13 expressions, whereas MUC2 expression was enhanced. Conclusions Both hydrochloric acid and deoxycholic acid could suppress Notch signaling pathway in esophageal epithelial cells, and inhibited Notch signaling has important functions in the development of Barrett's esophagus.
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