Acid and bile salt up-regulate BMP4 expression in human esophageal epithelium cells
Acid and bile salt up-regulate BMP4 expression in human esophageal epithelium cells
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DOI：
10.1080/00365520902998661
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发表时间：
2009-01
影响因子：
1.9
通讯作者：
Gang Zhou;Yong-gang Sun;Hong-Bin Wang;Wei-qiang Wang;Xing-wei Wang;D. Fang
中科院分区：
文献类型：
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作者：
Gang Zhou;Yong-gang Sun;Hong-Bin Wang;Wei-qiang Wang;Xing-wei Wang;D. Fang
Objective. Barrett食管（BE）的食管上皮是食管腺癌的癌前病变。Barrett化生的病理生理机制知之甚少。以往的研究认为多能细胞向柱状上皮分化可能是其机制之一。骨形态发生蛋白4（BMP 4），一个决定细胞命运的因子，与正常鳞状或不含杯状细胞的心脏上皮相比，在BE和食管炎粘膜中上调。本研究的目的是证明BMP 4是一种分子介质，它将BE的病原体与人食管上皮细胞（HEECs）的表型变化联系起来。材料和方法。采用原代培养的HEEC，观察酸和胆盐对BMP 4表达的影响，以及BMP 4对HEEC的生物学效应。结果酸和胆盐增加了BMP 4的表达。此外，重组人BMP 4诱导绒毛蛋白在HEEC中的表达，慢性酸暴露也是如此，这可以被BMP 4的特异性拮抗剂Noggin有效地抑制。Western印迹分析的结果表明，BMP 4诱导smad 1的活化并促进ID2和CDX2的蛋白表达。结论BMP 4在BE的发生发展中可能起重要作用。
Objective. Barrett's esophagus (BE) with an intestinal-type epithelium is thought to be a precancerous lesion of adenocarcinoma of the esophagus. The pathophysiology of Barrett's metaplasia is poorly understood. Previous studies suggest that differentiation of multipotent cells to columnar epithelium may be one of the possible mechanisms. Bone morphogenetic protein 4 (BMP4), a factor determining the fate of cells, is up-regulated in BE and esophagitis mucosa when compared with normal squamous or non-goblet cell-containing cardiac epithelium. The aim of this study was to demonstrate that BMP4 is a molecular mediator that links etiological agents of BE to the phenotypic changes in human esophagus epithelium cells (HEECs). Material and methods. Primary cultured HEECs were used to investigate the effect of acid and bile salt on BMP4 expression and to examine the biological effects of BMP4 on HEECs. Results. Acid and bile salt increased the expression of BMP4. In addition, recombinant human BMP4 induced villin expression in HEECs, as did chronic acid exposure, which can be effectively inhibited by Noggin, a specific antagonist of BMP4. Results from a Western blot assay suggest that BMP4 induces activation of smad1 and promotes protein expression of ID2 and CDX2. Conclusion. BMP4 may play an important role in the development of BE.