Journal
ONCOLOGY REPORTS
Volume 34, Issue 5, Pages 2674-2682Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2015.4207
Keywords
farnesoid X receptor; caudal-related homeobox transcription factor 2; mucin 2; deoxycholic acid; intestinal metaplasia; human gastric epithelial cells; NF-kappa B
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Funding
- National Natural Science Foundation of China [81200261]
- Science and Technology Fund Project of Tianjin Health Bureau [07K222]
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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.
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