Muramatsu Y, Fukushima K, Iino K, Totsune K, Takahashi K, Suzuki T, Hirasawa G, Takeyama J, Ito M, Nose M, Tashiro A, Hongo M, Oki Y, Nagura H, Sasano H
Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Peptides. 2000 Dec;21(12):1799-809. doi: 10.1016/s0196-9781(00)00335-1.
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. Urocortin 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 1 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.
促肾上腺皮质激素释放因子相关肽是促肾上腺皮质激素释放因子（CRF）神经肽家族新发现的成员。已发现促肾上腺皮质激素释放因子相关肽能与CRF受体高亲和力结合。本研究调查了促肾上腺皮质激素释放因子相关肽及CRF受体在人结肠黏膜中的表达。手术时从结直肠癌患者获取成人结直肠组织的非病理切片。采用免疫组织化学和信使（m）RNA原位杂交检测促肾上腺皮质激素释放因子相关肽的表达。还通过流式细胞术分析分离的固有层单核细胞（LPMC）和上皮细胞，以鉴定促肾上腺皮质激素释放因子相关肽阳性细胞，并通过逆转录聚合酶链反应（RT-PCR）检测促肾上腺皮质激素释放因子相关肽、CRF及CRF受体mRNA。利用手术和尸检标本，通过免疫组织化学检查促肾上腺皮质激素释放因子相关肽在人类不同发育阶段（n = 35，从妊娠11周龄至6岁）的分布情况。免疫反应性促肾上腺皮质激素释放因子相关肽和促肾上腺皮质激素释放因子相关肽mRNA主要在固有层巨噬细胞中检测到。促肾上腺皮质激素释放因子相关肽的表达最早在3月龄时检测到，但出生前或新生儿期未检测到。在LPMC中检测到促肾上腺皮质激素释放因子相关肽、1型和2型α CRF受体mRNA。2型β CRF受体mRNA是人类组织中的一种次要亚型，也在LPMC中检测到，但水平较低。促肾上腺皮质激素释放因子相关肽在固有层巨噬细胞中局部合成，并可能作为黏膜免疫系统的自分泌/旁分泌调节因子作用于固有层炎症细胞。出生后促肾上腺皮质激素释放因子相关肽的出现表明，出生后接触饮食摄入物和/或管腔细菌可能有助于人类胃肠道黏膜中促肾上腺皮质激素释放因子相关肽表达的启动。
