Influence of acid and bile acid on ERK activity, PPAR_Y expression and cell proliferation in normal human esophageal epithelial cells

AIM: To observe the effects of acid and bile acid exposure on cell proliferation and the expression of extracellular signal-regulated protein kinase (ERK) and peroxisome proliferator-activated receptor Y (PPAR_Y) in normal human esophageal epithelial cells in vitro. METHODS: In vitro cultured normal human esophageal epithelial cells were exposed to acidic media (pH 4.0-6.5), media containing different bile acid (250μmol/ L), media containing acid and bile acid, respectively. Cell proliferation was assessed using MTT and flow cytometry. The expressions of phosphorylated ERK1/2 and PPAR_Y protein were determined by the immunoblotting technique. RESULTS: Acid-exposed (3 min) esophageal cells exhibited a significant increase in proliferation ratio, S phase of the cell cycle (P<0.05) and the level of phosphorylated ERK1/2 protein. When the acid-exposure period exceeded 6 min, we observed a decrease in proliferation ratio and S phase of the cell cycle, with an increased apoptosis ratio (P<0.05). Bile acid exposure (3-12 min) also produced an increase in proliferation ratio, S phase of the cell cycle (P<0.05) and phosphorylated ERK1/2 expression. On the contrary, deoxycholic acid (DCA) exposure (> 20 min) decreased proliferation ratio. Compared with bile acid exposure (pH 7.4), bile acid exposure (pH 6.5, 4) significantly decreased proliferation ratio (P<0.05). There was no expression of PPAR_Y in normal human esophageal epithelial cells. CONCLUSION: The rapid stimuli of acid or bile acid increase proliferation in normal human esophageal epithelial cells by activating the ERK pathway.

Influence of acid and bile acid on ERK activity, PPARY expression and cell proliferation in normal human esophageal epithelial cells

AIM: To observe the effects of acid and bile acid exposure on cell proliferation and the expression of extracellular signal-regulated protein kinase (ERK) and peroxisome proliferator-activated receptor Y (PPARy) in normal human esophageal epithelial cells in vitro.METHODS: In vitro cultured normal human esophageal epithelial cells were exposed to acidic media (pH 4.0-6.5), media containing different bile acid (250 μmol/L), media containing acid and bile acid, respectively.Cell proliferation was assessed using MTT and flow cytometry. The expressions of phosphorylated ERK1/2 and PPARy protein were determined by the immunoblotting technique.RESULTS: Acid-exposed (3 min) esophageal cells exhibited a significant increase in proliferation ratio,S phase of the cell cycle (P＜0.05) and the level of phosphorylated ERK1/2 protein. When the acid-exposure period exceeded 6 min, we observed a decrease in proliferation ratio and S phase of the cell cycle, with an increased apoptosis ratio (P＜0.05). Bile acid exposure (3-12 min) also produced an increase in proliferation ratio, S phase of the cell cycle (P＜0.05)and phosphorylated ERK1/2 expression. On the contrary,deoxycholic acid (DCA) exposure (＞20 min) decreased proliferation ratio. Compared with bile acid exposure (pH 7.4), bile acid exposure (pH 6.5, 4) significantly decreased proliferation ratio (P＜0.05). There was no expression of PPARY in normal human esophageal epithelial cells.CONCLUSION: The rapid stimuli of acid or bile acid increase proliferation in normal human esophageal epithelial cells by activating the ERK pathway.