Cell lineage dynamics in the process leading to intestinal metaplasia
Cell lineage dynamics in the process leading to intestinal metaplasia
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DOI：
10.1007/s00535-011-0391-0
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发表时间：
2011-03
影响因子：
6.3
通讯作者：
H. Sakamoto;H. Mutoh;Hiroko Hayakawa;M. Sashikawa;K. Sugano
中科院分区：
文献类型：
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作者：
H. Sakamoto;H. Mutoh;Hiroko Hayakawa;M. Sashikawa;K. Sugano
背景在人胃粘膜肠上皮化生转变的早期阶段基因表达尚未确定。在这项研究中，我们研究了细胞谱系变化和大肠杆菌特异性基因表达之间的时间关系，在导致肠化生的过程中，使用Cdx 2转基因小鼠。MethodsCells细胞表型进行了分析，免疫组化和比较细胞谱系标记物的基因表达谱，通过实时聚合酶链反应。Cdx 2转基因小鼠的胃粘膜在组织学上与其正常同窝小鼠的胃粘膜相似。然而，在大约PD 20时，我们观察到腺体零星出现，其中所有上皮细胞表达Cdx 2（Cdx 2-弥漫性阳性腺体）。在Cdx 2-弥漫阳性腺体中，壁细胞已消失，增殖区已从峡部移到基部，并识别出吸收细胞和杯状细胞。相反，周围粘膜保留胃腺的表型，其中只有一些上皮细胞表达Cdx 2。在PD 30和40期间，整个胃底粘膜变为转分化粘膜，其是肠化生和痉挛性多肽表达化生的复合物。在胃特异性基因表达的增加，与胃特异性基因表达的相互减少，开始远远早于Cdx 2-弥漫性阳性glands.ConclusionsA显着增加在胃特异性基因表达的肠化生和痉挛性多肽表达化生的形态外观之前出现。
BackgroundGene expression in the early stage of the transition to intestinal metaplasia in human gastric mucosa has not been determined. In this study, we investigated the temporal relationship between cell lineage changes and intestine-specific gene expression in the process leading to intestinal metaplasia, using Cdx2-transgenic mice.MethodsCellular phenotypes were analyzed by immunohistochemistry and were compared with the gene expression profiles of cell lineage markers by real-time polymerase chain reaction.ResultsUp to postnatal day (PD) 20, the gastric mucosae of Cdx2-transgenic mice were histologically similar to those of their normal littermates. However, at approximately PD 20, we observed the sporadic appearance of glands in which all the epithelial cells expressed Cdx2 (Cdx2-diffuse positive glands). In the Cdx2-diffuse positive glands, parietal cells had disappeared, the proliferating zone had moved from the isthmus to the base, and absorptive cells and goblet cells were recognized. In contrast, the surrounding mucosa retained the phenotype of the gastric gland in which only some of the epithelial cells expressed Cdx2. During PDs 30 and 40, the entire fundic mucosa changed to transdifferentiated mucosa that was a composite of intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia. An increase in the expression of intestine-specific genes, with a reciprocal decrease in gastric-specific gene expression, began much earlier than the emergence of Cdx2-diffuse positive glands.ConclusionsA dramatic increase in intestine-specific gene expression precedes the morphological appearance of intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia.