Farnesoid X receptor signal is involved in deoxycholic acid-induced intestinal metaplasia of normal human gastric epithelial cells
Farnesoid X receptor signal is involved in deoxycholic acid-induced intestinal metaplasia of normal human gastric epithelial cells
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DOI：
10.3892/or.2015.4207
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发表时间：
2015-11-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Bang-Mao
中科院分区：
文献类型：
--
作者：
Li, Shu;Chen, Xin;Wang, Bang-Mao
法尼醇X受体(FXR)信号通路参与胆汁酸、葡萄糖和脂肪的代谢。在本研究中，我们证实了400MU/L脱氧胆酸刺激能促进正常人胃上皮细胞的增殖。此外，DCA还激活了FXR，增加了尾端相关同源盒转录因子2(CDX2)和粘蛋白2(MUC2)等肠化生基因的表达。FXR激动剂GW4064/拮抗剂Guggulsterone(Guggulsterone，GUG)处理后，DCA诱导的GES-1细胞FXR、CDX2和MUC2蛋白表达水平显著升高/降低。GW4064/Gug.还增强/降低了核因子-kappa B(nf-kappa B)的活性和cdx2启动子区域与最常见的p50蛋白亚单位nf-kappa B的结合。综上所述，这些结果表明DCA能够通过核受体FXR-NF-kappa B的活性来调节正常胃上皮细胞CDX2及其下游MUC2的表达。因此，FXR信号通路可能参与了人胃粘膜肠化生。
The farnesoid X receptor (FXR) signaling pathway is known to be involved in the metabolism of bile acid, glucose and lipid. In the present study, we demonstrated that 400 mu mol/l deoxycholic acid (DCA) stimulation promotes the proliferation of normal human gastric epithelial cells (GES-1). In addition, DCA activated FXR and increased the expression of intestinal metaplasia genes, including caudal-related homeobox transcription factor 2 (Cdx2) and mucin 2 (MUC2). The treatment of FXR agonist GW4064/antagonist guggulsterone (Gug) significantly increased/decreased the expression levels of FXR, Cdx2 and MUC2 protein in DCA-induced GES-1 cells. GW4064/Gug. also enhanced/reduced the nuclear factor-kappa B (NF-kappa B) activity and binding of the Cdx2 promoter region and NF-kappa B, the most common subunit p50 protein. Taken together, the results indicated that DCA is capable of modulating the expression of Cdx2 and the downstream MUC2 via the nuclear receptor FXR-NF-kappa B activity in normal gastric epithelial cells. FXR signaling pathway may therefore be involved in the intestinal metaplasia of human gastric mucosa.