Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa

Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa
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DOI:
10.1016/s0196-9781(00)00335-1
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发表时间:
2000-12-01
期刊:
影响因子:
3
通讯作者:
Sasano, H
Sasano, H
中科院分区:
医学3区
文献类型:
--
作者:
Muramatsu, Y;Fukushima, K;Sasano, H

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尿皮质素是新发现的CRF神经肽家族成员。尿皮质素已被发现与CRF受体具有高亲和力结合,本研究研究了尿皮质素和CRF受体在人结肠粘膜中的表达。从结直肠癌手术患者获得成人结直肠组织的非病理切片。采用免疫组织化学和信使RNA原位杂交技术检测Urocorlin的表达。分离的固有层单个核细胞(LPMC)和上皮细胞也通过流式细胞术分析尿皮质素阳性细胞的特征,并通过RT-PCR检测尿皮质素、CRF和CRF受体mRNA。利用手术和尸检标本,通过免疫组织化学方法检测尿皮质素肽在人类发育不同阶段(n = 35,从妊娠11周到6岁)的分布。免疫反应性尿皮质素和尿皮质素mRNA主要在固有层巨噬细胞中检测到。早在3个月大的时候就可以检测到尿皮质素肽的表达,但在出生前或新生儿中没有检测到。在LPMC中检测尿皮质素、CRF受体类型和2型α mRNA。CRF受体2型β mRNA是人体组织中的一种次要亚型,在LPMC中也检测到,但水平较低。尿皮质素在固有层巨噬细胞中局部合成,并可能作为粘膜免疫系统的自分泌/旁分泌调节剂作用于固有层炎症细胞。出生后尿皮质素的出现表明,出生后暴露于饮食摄入和/或肠道细菌可能有助于启动尿皮质素在人类胃肠道粘膜中的表达。(C) 2000 Elsevier Science Inc.;版权所有。
Urocortin is a newly identified member of the CRF neuropeptide family. Urocortin has been found to bind with high affinity to CRF receptors, The present study investigated urocortin and CRF receptor expression in human colonic mucosa. Non-pathologic sections of adult colorectal tissues were obtained from patients with colorectal cancer at surgery. Urocorlin expression was examined using immunohistochemistry and messenger (m) RNA in situ hybridization. Isolated lamina propria mononuclear cells (LPMC) and epithelial cells were also analyzed by flow cytometry for the characterization of urocortin-positive cells, and by RT-PCR for detection of urocortin, CRF, and CRF receptor mRNA. Urocortin peptide distribution at various stages of human development (n = 35, from 11 weeks of gestation to 6 years of age) was examined by immunohistochemistry using surgical and autopsy specimens. Immunoreactive urocortin and urocortin mRNA were predominantly detected in lamina propria macrophages. Urocortin peptide expression was detected from as early as three months of age, but not before birth or in neonates. Urocortin, CRF receptor type and type 2 alpha mRNA were detected in LPMC. CRF receptor type 2 beta mRNA, a minor isoform in human tissues, was also detected in LPMC, but at lower levels. Urocortin is locally synthesized in lamina propria macrophages and may act on lamina propria inflammatory cells as an autocrine/paracrine regulator of the mucosal immune system. The appearance of urocortin after birth indicates that the exposure to dietary intake and/or luminal bacteria after birth may contribute to the initiation of urocortin expression in human gastrointestinal tract mucosa. (C) 2000 Elsevier Science Inc. All rights reserved.