Zhi-Ru Jiang1, Jun Gong, Zhen-Ni Zhang, Zhe Qiao. 1. Department of Gastroenterology, Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China. jiangzhr@21cn.com
Abstract
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 gamma (PPARgamma) 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 mumol/L), media containing acid and bile acid, respectively. Cell proliferation was assessed using MTT and flow cytometry. The expressions of phosphorylated ERK(1/2) and PPARgamma 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 ERK(1/2) 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 ERK(1/2) 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 PPARgamma 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.
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 gamma (PPARgamma) 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 mumol/L), media containing acid and bile acid, respectively. Cell proliferation was assessed using MTT and flow cytometry. The expressions of phosphorylated ERK(1/2) and PPARgamma 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 ERK(1/2) 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 ERK(1/2) 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 PPARgamma 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.