The intestine-specific homeobox gene Cdx2 induces expression of the basic helix-loop-helix transcription factor Math1
The intestine-specific homeobox gene Cdx2 induces expression of the basic helix-loop-helix transcription factor Math1
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DOI：
10.1111/j.1432-0436.2006.00074.x
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发表时间：
2006-07-01
期刊：
影响因子：
2.9
通讯作者：
Sugano, K
中科院分区：
文献类型：
--
作者：
Mutoh, H;Sakamoto, H;Sugano, K
基本的螺旋-环-螺旋转录因子Math1，在发育中的神经系统多个区域的增殖神经前体中短暂表达，也与肠内分泌、杯状细胞和肠内Paneth细胞的命运决定有关。另一方面，通常局限于肠上皮细胞的转录因子Cdx2与肠上皮细胞的分化有关。因此，我们研究了肠上皮细胞中Math1和Cdx2的关系。采用免疫组化、逆转录聚合酶链反应和Northern印迹法分析了Math1和Cdx2在小鼠和人胃正常肠黏膜、肠化生粘膜以及肠隐窝来源细胞系中的表达，采用荧光素酶报告基因法分析了Math1增强子元素的表达。在人和小鼠的正常肠黏膜中均发现了共表达Cdx2的math1阳性上皮细胞。此外，在人和Cdx2转基因小鼠的肠化生黏膜中也发现了Cdx2免疫染色阳性的产生math1的上皮细胞，尽管在人和小鼠的正常胃黏膜中未发现。Cdx2的表达刺激肠隐窝来源细胞系IEC-6中内源性Math1 mRNA的表达，证实了在表达Cdx2的肠化生粘膜中的观察结果。此外，Cdx2在IEC-6细胞中的表达赋予了表达包含Math1增强子的Math1报告基因的能力。基于这些结果，我们假设Cdx2参与激活肠上皮细胞中Math1的表达。
The basic helix-loop-helix transcription factor Math1, which is transiently expressed in proliferating neural precursors in multiple domains of the developing nervous system, is also related to the cell fate decision of enteroendocrine, goblet, and Paneth cells in the intestine. On the other hand, the transcription factor Cdx2, which is normally confined to intestinal epithelial cells, is related to the differentiation of these cells. Therefore, we investigated the relationship between Math1 and Cdx2 in intestinal epithelial cells. The Math1 and Cdx2 expressions in normal intestinal mucosa and intestinal metaplastic mucosa from mouse and human stomachs, as well as an intestinal crypt-derived cell line, were analyzed by immunohistochemistry, reverse transcription-polymerase chain reaction and Northern blotting, and Math1 enhancer element was analyzed by luciferase reporter assays. Math1-positive epithelial cells co-expressing Cdx2 were found in normal intestinal mucosa from humans and mice. Furthermore, Math1-producing epithelial cells that showed positive immunostaining for Cdx2 were also observed in intestinal metaplastic mucosa from human and Cdx2 transgenic mouse stomachs, although they were not detected in normal gastric mucosa of humans and mice. Expression of Cdx2 stimulated endogenous Math1 mRNA expression in the intestinal crypt-derived cell line IEC-6, corroborating observations in Cdx2-expressing intestinal metaplastic mucosa. Furthermore, expression of Cdx2 in IEC-6 cells conferred the ability to express a Math1 reporter gene containing a Math1 enhancer. Based on these results, we hypothesize that Cdx2 is involved in activating Math1 expression in intestinal epithelial cells.