Zhou Gang, Sun Yong-Gang, Wang Hong-Bin, Wang Wei-Qiang, Wang Xing-Wei, Fang Dian-Chun
Department of Gastroenterology, Southwest Hospital, The Third Military Medical University, ChongQing, China.
Scand J Gastroenterol. 2009;44(8):926-32. doi: 10.1080/00365520902998661.
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).
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.
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.
BMP4 may play an important role in the development of BE.
具有肠型上皮的巴雷特食管（BE）被认为是食管腺癌的一种癌前病变。巴雷特化生的病理生理学尚不清楚。先前的研究表明，多能细胞向柱状上皮的分化可能是一种可能的机制。骨形态发生蛋白4（BMP4）是一种决定细胞命运的因子，与正常鳞状上皮或不含杯状细胞的贲门上皮相比，在BE和食管炎黏膜中上调。本研究的目的是证明BMP4是一种分子介质，它将BE的病因与人类食管上皮细胞（HEECs）的表型变化联系起来。
使用原代培养的HEECs来研究酸和胆盐对BMP4表达的影响，并检测BMP4对HEECs的生物学作用。
酸和胆盐增加了BMP4的表达。此外，重组人BMP4在HEECs中诱导了绒毛蛋白的表达，慢性酸暴露也有同样的作用，而这可以被BMP4的特异性拮抗剂Noggin有效抑制。蛋白质印迹分析结果表明，BMP4诱导smad1的激活，并促进ID2和CDX2的蛋白表达。
BMP4可能在BE的发生发展中起重要作用。
