The role of p38 signal transduction pathway in the pathogenesis of Barrett esophagus / 中华消化杂志

ABSTRACT

Objective To investigate the role of deoxycholic acid (DCA) in the pathogenesis of Barrett esophagus.Methods Normal human esophageal mucosal epithelial cells were cultured in vitro with defined keratinocyte serum-free media (D-KSFM).The cultured cells were treated with different concentrations of DCA and specific p38 mitogen activated protein kinase (MAPK) inhibitor. The expression of p38,phosphorylated p38 (p-p38) and caudal-related homeodomain transcription 2 (CDX2) at protein level were assessed by Western blot.The correlation between p-p38 and CDX2 was analyzed.The data were analyzed by one way ANOVA and LSD test.Results After being cultured with DCA for 24 h,the expression of p-p38 and CDX2 increased along with the increasing of DCA concentration.Compared with the control group (p-p38 was 13.7％ ± 1.0％ and CDX2 protein was 0),the difference was statistically significant (P＜ 0.05).When DCA was at 500 μmol/L,the expression of p-p38 and CDX2 reached the highest level (44.0％ ± 1.7％ and 8.59± 1.25).After pretreated with SB203580 for two hours and then 500 μmol/L DCA was added into cell culture,both expression level of p-p38 and CDX2 decreased compared with 500μmol/L DCA group (p-p38:28.3％ ±2.2％ vs50.5％±9.5％,CDX2:0.94±0.13 vs 2.31±0.41) after 24 h.Conclusions DCA can induce the expression of CDX2 in normal human esophageal mucosal epithelial cells,which is related with the activation of p38.The phosphorylation of p38 maybe involved in the pathogenesis of Barrett esophagus.