Neurocrine Biosciences Inc., San Diego, CA 92121, USA.
World J Gastroenterol. 2013 Mar 7;19(9):1416-23. doi: 10.3748/wjg.v19.i9.1416.
To assess corticotropin-releasing factor receptor 2 (CRF2) expression in the colon of healthy subjects and patients with ulcerative colitis (UC).
We examined CRF2 gene and protein expression in the distal/sigmoid colonic mucosal biopsies from healthy subjects and patients with UC (active or disease in remission), human immunodeficiency virus (HIV) and functional bowel disease (FBD) by reverse transcription-polymerase chain reaction and immunofluorescence.
Gene expression of CRF2 was demonstrated in the normal human colonic biopsies, but not in the human colorectal adenocarcinoma cell line Caco2. Receptor protein localization showed immunoreactive CRF2 receptors in the lamina propria and in the epithelial cells of the distal/sigmoid biopsy samples. Interestingly, CRF2 immunoreactivity was no longer observed in epithelial cells of patients with mild-moderately active UC and disease in remission, while receptor protein expression did not change in the lamina propria. No differences in CRF2 expression profile were observed in distal/sigmoid intestinal biopsies from HIV infection and FBD patients, showing no signs of inflammation.
The down-regulation of the CRF2 receptor in the distal/sigmoid biopsies of UC patients is indicative of change in CRF2 signalling associated with the process of inflammation.
评估健康受试者和溃疡性结肠炎(UC)患者结肠中促肾上腺皮质素释放因子受体 2(CRF2)的表达。
我们通过逆转录-聚合酶链反应和免疫荧光技术,检测了健康受试者和 UC(活动期或缓解期)、人类免疫缺陷病毒(HIV)和功能性肠病(FBD)患者的远端/乙状结肠黏膜活检中 CRF2 基因和蛋白的表达。
CRF2 基因在正常的人类结肠活检中表达,但在人结直肠腺癌细胞系 Caco2 中不表达。受体蛋白定位显示,在远端/乙状结肠活检样本的固有层和上皮细胞中存在免疫反应性的 CRF2 受体。有趣的是,在轻度至中度活动期 UC 和缓解期的患者的上皮细胞中,不再观察到 CRF2 免疫反应性,而固有层中的受体蛋白表达没有变化。在 HIV 感染和 FBD 患者的远端/乙状结肠活检中,CRF2 表达谱没有差异,没有炎症迹象。
UC 患者远端/乙状结肠活检中 CRF2 受体的下调表明与炎症过程相关的 CRF2 信号发生变化。