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World J Gastroenterol. Apr 21, 2006; 12(15): 2445-2449
Published online Apr 21, 2006. doi: 10.3748/wjg.v12.i15.2445
Influence of acid and bile acid on ERK activity, PPARγ expression and cell proliferation in normal human esophageal epithelial cells
Zhi-Ru Jiang, Jun Gong, Zhen-Ni Zhang, Zhe Qiao
Zhi-Ru Jiang, Jun Gong, Department of Gastroenterology, Second Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Zhen-Ni Zhang, Department of Anesthesiology, Second Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Zhe Qiao, Department of Thoracic Surgery, Second Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Correspondence to: Zhi-Ru Jiang, Department of Gastroen-terology, Second Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China. jiangzhr@21cn.com
Telephone: +86-29-81042024
Received: December 6, 2005
Revised: January 2, 2006
Accepted: January 14, 2006
Published online: April 21, 2006
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 γ (PPARγ) 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 PPARγ 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 PPARγ 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.

Keywords: Acid; Bile acid; Esophageal epithelial cells; Cell proliferation; Extracellular signal-regulated protein kinase