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

机译:酸和胆汁酸对正常人食管上皮细胞ERK活性PPARγ表达和细胞增殖的影响

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摘要

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.
机译:目的:观察酸和胆汁酸暴露对正常人食管上皮细胞增殖和细胞外信号调节蛋白激酶(ERK)和过氧化物酶体增殖物激活受体γ(PPARγ)表达的影响。将体外培养的正常人食管上皮细胞暴露于酸性培养基(pH 4.0±6.5),含有不同胆汁酸的培养基(250μmol/ L),含有酸和胆汁酸的培养基。使用MTT和流式细胞术评估细胞增殖。结果:经酸暴露(3min)的食管细胞增殖率,细胞周期的S期(P <0.05)和表达水平显着提高。磷酸化的ERK1 / 2蛋白。当酸暴露时间超过6分钟时,我们观察到细胞周期的增殖率和S期降低,凋亡率增加(P <0.05)。胆汁酸暴露(3-12分钟)也使增殖率,细胞周期的S期(P <0.05)和磷酸化的ERK1 / 2表达增加。相反,脱氧胆酸(DCA)暴露(> 20分钟)会降低增殖率。与胆汁酸暴露(pH 7.4)相比,胆汁酸暴露(pH 6.5、4)显着降低了增殖率(P <0.05)。结论正常人食管上皮细胞中没有PPARγ的表达。结论:酸或胆汁酸的快速刺激通过激活ERK途径增加了正常人食管上皮细胞的增殖。

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