Deoxycholic acid (DCA) confers an intestinal phenotype on esophageal squamous epithelium via induction of the stemness-associated reprogramming factors OCT4 and SOX2

Deoxycholic acid (DCA) confers an intestinal phenotype on esophageal squamous epithelium via induction of the stemness-associated reprogramming factors OCT4 and SOX2
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脱氧胆酸 (DCA) 通过诱导干性相关重编程因子 OCT4 和 SOX2 赋予食管鳞状上皮肠道表型

DOI:
10.1080/15384101.2016.1175252
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发表时间:
2016-04
期刊:
影响因子:
4.3
通讯作者:
Fang, Dianchun
Fang, Dianchun
中科院分区:
生物学3区
文献类型:
--
作者:
Yan, Wu;Xia, Yiju;Hu, Jiali;Fang, Dianchun

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摘要Barrett食管(BE)实质上是一种上皮化生,其中正常的复层鳞状上皮被柱状上皮所取代。这项研究的重点是参与OCT 4和SOX 2,2个关键的细胞重编程因子,在脱氧胆酸(DCA)诱导的表达的肠道标志Cdx 2和MUC 2使用在体内和体外模型。与正常食管和食管炎相比,OCT 4在BE中表达上调,SOX 2表达下调。与体内数据一致,DCA在mRNA和蛋白质水平诱导OCT 4的时间依赖性表达,并降低Het-1A细胞中SOX 2的核表达。通过siRNA下调OCT 4表达废除了DCA诱导的Cdx 2和MUC 2的表达,而针对SOX 2的siRNA显著上调Cdx 2和MUC 2的表达。我们的数据表明,OCT 4和SOX 2在胆汁酸反流触发的BE的发展中起重要作用。
ABSTRACT Barrett's esophagus (BE) is essentially a metaplasia in which the normal stratified squamous epithelium is replaced by columnar epithelium. This study focuses on the involvement of OCT4 and SOX2, 2 key cell-reprogramming factors, in the deoxycholic acid (DCA)-induced expression of the intestinal hallmarks Cdx2 and MUC2 using both in vivo and in vitro models. Up-regulated expression of OCT4 and down-regulated expression of SOX2 were observed in BE compared with normal esophagus and esophagitis. Consistent with the data in vivo, DCA induced time-dependent expression of OCT4 at both the mRNA and protein levels and decreased nuclear expression of SOX2 in Het-1A cells. Down-regulation of OCT4 expression by siRNA abrogated DCA-induced expression of Cdx2 and MUC2, whereas siRNA against SOX2 significantly upregulated the expression of both Cdx2 and MUC2. Our data indicate that both OCT4 and SOX2 play important roles in the development of BE triggered by bile acid reflux.
发展。食管干细胞,您在哪里?
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