脱氧胆酸在酸性环境下促进正常食管鳞状上皮细胞表达BMP4

Deoxycholic Acid Induces BMP4 Expression in Normal Esophageal Squamous Cells under Acidic pH in vitro

背景:骨形态发生蛋白4(BMP4)是Barrett食管(BE)上皮的标记性蛋白,可调节CDX2表达以及促进肠化生,但其在BE中表达上调的机制尚不明脱氧胆酸(DCA)是BE发生的重要环境因素。目的:探讨DCA对正常食管鳞状上皮细胞BMP4及其第二信使Smadl表达的影响方法:培养原代正常食管鳞状上皮细胞,采用不同浓度DCA与pH值酸处理细胞。分别以实时荧光定量聚合酶链反应(PCR)和蛋白质印迹法检测BMP4、Smadl mRNA和蛋白表达。结果:DCA在酸性环境下可呈浓度依赖性地增性正常食管鳞状上皮细胞表达BMP4,同时100μmol/L DCA可促进Smadl表达,200μmol/L

Background： Bone morphogenetic protein 4 （BMP4） is a biologic marker of Barrett＇s esophagus （BE）. BMP4 can regulate CDX2 expression and promote intestinal metaplasia, but the mechanism of up-regulation of BMP4 expression in BE is still unknown. Deoxycholie acid （DCA） is an important environmental factor in the occurrence of BE. Aims： To investigate the effect of DCA on BMP4 and its second messenger Smadl in normal esophageal squamous ceils. Methods： Primary normal esophageal squamous cells were cultured, and then under different concentrations of DCA and pH value. The mRNA and protein expressions of BMP4, Smadl were examined by real-time fluorescent quantitative polymerase chain reaction （PCR） and Western blotting, respectively. Results： DCA at acidic pH dose-dependent increased the expression of BMP4 in normal esophageal squamous ceils. Meanwhile, DCA at 100 μmol/L up-regulated Smadl expression, but downregulated Smadl expression at 200 μmol/L. Conclusions： DCA can regulate BMP4 and Smadl expressions, and may play a role in the development of BE.