Farnesoid X receptor signal is involved in deoxycholic acid-induced intestinal metaplasia of normal human gastric epithelial cells.
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 µmol/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-κB (NF-κB) activity and binding of the Cdx2 promoter region and NF-κB, 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-κB activity in normal gastric epithelial cells. FXR signaling pathway may therefore be involved in the intestinal metaplasia of human gastric mucosa.
Department of Gastroenterology and Hepatology, Tianjin General Hospital, Tianjin Medical University, Heping, Tianjin 300052, P.R. China.
Shu
S
Li
Department of Gastroenterology and Hepatology, Tianjin General Hospital, Tianjin Medical University, Heping, Tianjin 300052, P.R. China.
Xin
X
Chen
Department of Gastroenterology and Hepatology, Tianjin General Hospital, Tianjin Medical University, Heping, Tianjin 300052, P.R. China.
Lu
L
Zhou
Department of Gastroenterology and Hepatology, Tianjin General Hospital, Tianjin Medical University, Heping, Tianjin 300052, P.R. China.
Bang-Mao
BM
Wang
D000071616:CDX2 Transcription Factor; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000473:pathology; D007555:Isoxazoles / Q000494:pharmacology; D008679:Metaplasia; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000099150:Receptor, Farnesoid X-Activated
D000071616:CDX2 Transcription Factor; D003840:Deoxycholic Acid; D018398:Homeodomain Proteins; D007555:Isoxazoles; D055262:Mucin-2; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C491270:CDX2 protein, human; C524625:MUC2 protein, human; C412815:GW 4064