Pathogenesis of Barrett esophagus - Deoxycholic acid up-regulates goblet-specific gene MUC2 in concert with CDX2 in human esophageal cells
Pathogenesis of Barrett esophagus - Deoxycholic acid up-regulates goblet-specific gene MUC2 in concert with CDX2 in human esophageal cells
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DOI：
10.1001/archsurg.142.6.540
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发表时间：
2007-06-01
影响因子：
--
通讯作者：
Peters, Jeffrey H.
中科院分区：
文献类型：
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作者：
Hu, Yingchuan;Jones, Carolyn;Peters, Jeffrey H.
假设：接触胆汁酸可以。诱导尾端相关同源盒2(CDX2)信使RNA(MRNA)的表达，这是一种在Barrett食道发育中起关键作用的转录因子。我们研究了脱氧胆酸处理前后4个人食道细胞系中粘蛋白2(MUC2)和CDX2 mRNA的表达。设计、背景和对象：4个人食道细胞系-(1)用SV40(Het-1A)永生化的正常鳞状细胞，(2)腺癌。(SEG-1)和(3和4)鳞状细胞癌(HKESC-1和HKESC-2)-在培养1~24小时至100亩M至1000亩M脱氧胆酸。主要观察指标：半定量逆转录聚合酶链式反应检测MUC2和CDX2mRNA的表达。结果：4种细胞株在脱氧胆酸处理前均未见MUC2的表达。在所有细胞系中，经脱氧胆酸处理后，MUC2的表达均呈剂量和时间依赖性增加。结论：胆汁酸可上调正常食管腺癌细胞和癌细胞系的肠道分化因子CDX2和杯状细胞特异性基因MUC2的表达。此外，胆汁酸刺激的MUC2上调与CDX2上调直接相关。胆汁酸暴露后CDX2和MUC2同时上调，为胆汁酸在Barrett食道发病机制中的作用提供了分子证据。
Hypothesis: Bile acid exposure can. induce caudal-related homeobox 2 (CDX2) messenger RNA (mRNA) expression, a transcription factor that plays a crucial role in the development of Barrett esophagus. We investigated mucin 2 (MUC2) and CDX2 mRNA expression before and after treatment with deoxycholic acid in 4 human esophageal cell lines.Design, Setting, and Participants: Four human esophageal cell lines-(1) normal squamous cells immortalized by SV40 (Het-1A), (2) adenocarcinoma. (SEG-1), and (3 and 4) squamous cell carcinoma (HKESC-1 and HKESC-2)-were exposed in culture for 1 to 24 hours to 100 mu M to 1000 mu M deoxycholic acid. Total RNA was extracted before and after bile acid treatment and reverse transcribed to complementary DNA.Main Outcome Measure: MUC2 and CDX2 mRNA expression as determined by semiquantitative reverse transcription-polymerase chain reaction.Results: MUC2 mRNA expression was absent before deoxycholic acid exposure in all 4 cell lines. MUC2 expression increased in a dose- and time-dependent manner with deoxycholic acid in all cell lines. Deoxycholic acid activated MUC2 up-regulation, which correlated directly with CDX2 up-regulation in all 4 cell lines.Conclusions: Bile acids up-regulate both intestinal differentiation factor CDX2 and goblet cell-specific gene MUC2 in normal esophageal and cancer cell lines. Further, bile acid-stimulated MUC2 up-regulation correlates directly with CDX2 up-regulation. The simultaneous up-regulation of both CDX2 and MUC2 after bile acid exposure provides molecular evidence of the role of bile acid in the pathogenesis of Barrett esophagus.