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


CONCLUSIONS
The rapid stimuli of acid or bile acid increase proliferation in normal human esophageal epithelial cells by activating the ERK pathway.
Jiang
Zhi-Ru
ZR
Department of Gastroenterology, Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China. jiangzhr@21cn.com
Gong
Jun
J
Zhang
Zhen-Ni
ZN
Qiao
Zhe
Z