EP receptor expression in human intestinal epithelium and localization relative to the stem cell zone of the crypts.

EP receptor expression in human intestinal epithelium and localization relative to the stem cell zone of the crypts.
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DOI:
10.1371/journal.pone.0026816
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Lea T
Lea T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Olsen Hult LT;Kleiveland CR;Fosnes K;Jacobsen M;Lea T

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有大量证据表明 PGE2 影响肠上皮增殖。据报道,PGE2 还参与成体干细胞生长和分化的调节,这两种作用都是通过与 EP 受体结合介导的。我们使用 Lgr5 作为标记来仔细检查人肠上皮细胞中的 EP 受体和 COX 表达,重点关注隐窝的干细胞区域。通过免疫组织化学和 RT-PCR 对来自回肠和结肠的正常组织以及未经治疗的乳糜泻患者的十二指肠活检进行了研究。新鲜速冻组织和激光显微切割相结合,使得仅从上皮细胞层分离 RNA 成为可能。在小肠中,Lgr5 标记细胞位于 +4 位置,而在结肠中,Lgr5 阳性细胞位于隐窝底部。正常小肠的上皮隐窝细胞既不表达EP受体mRNA也不表达COX1/2。然而,未经治疗的乳糜泻患者组织中的隐窝细胞表达 EP2/4 受体和 COX1 mRNA。在结肠中,情况有所不同。发现来自正常结肠的上皮隐窝细胞表达 EP2/4 受体和 COX1/2 转录物。因此,正常人小肠和结肠之间在EP2/4受体和COX1/2的表达方面存在明显差异。在正常结肠组织中,PGE2通过EP受体2/4介导的信号传导可能参与上皮生长和分化的调节,而小肠组织中EP受体表达的缺乏排除了PGE2对隐窝上皮细胞直接作用的可能性。
There is substantial evidence for PGE2 affecting intestinal epithelial proliferation. PGE2 is also reported to be involved in the regulation of growth and differentiation in adult stem cells, both effects mediated by binding to EP-receptors. We have used the Lgr5 as a marker to scrutinize EP-receptor and COX expression in human intestinal epithelial cells with focus on the stem cell area of the crypts. Normal tissue from ileum and colon, but also duodenal biopsies from patients with untreated celiac disease, were investigated by immunohistochemistry and RT-PCR. The combination of fresh flash-frozen tissue and laser microdissection made it possible to isolate RNA from the epithelial cell layer, only. In the small intestine, Lgr5 labels cells are in the +4 position, while in the colon, Lgr5 positive cells are localized to the crypt bottoms. Epithelial crypt cells of normal small intestine expressed neither EP-receptor mRNA nor COX1/2. However, crypt cells in tissue from patients with untreated celiac disease expressed EP2/4 receptor and COX1 mRNA. In the colon, the situation was different. Epithelial crypt cells from normal colon were found to express EP2/4 receptor and COX1/2 transcripts. Thus, there are distinct differences between normal human small intestine and colon with regard to expression of EP2/4 receptors and COX1/2. In normal colon tissue, PGE2-mediated signaling through EP-receptors 2/4 could be involved in regulation of growth and differentiation of the epithelium, while the lack of EP-receptor expression in the small intestinal tissue exclude the possibility of a direct effect of PGE2 on the crypt epithelial cells.
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