Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
Exp Mol Pathol. 2013 Aug;95(1):111-6. doi: 10.1016/j.yexmp.2013.06.004. Epub 2013 Jun 14.
C-X-C chemokine receptor type 4 (CXCR4) plays a crucial role in a wide range of physiological and pathological processes, including the migration of stem cells, such as neural crest-derived cells. Hirschsprung's disease (HSCR), a developmental disorder characterized by the absence of ganglion cells, is regarded as the consequence of the premature arrest of the craniocaudal migration of neural crest-derived cells (NCDCs) in the gastrointestinal tract during the development of the enteric nervous system (ENS). In this study, colon tissue samples from 61 HSCR patients were surgically collected and divided into aganglionic, oligoganglionic and normal ganglionic segments. Quantitative real-time polymerase chain reactions (PCR), Western blotting, and immunohistochemical and immunofluorescence staining were performed to analyze the expression levels and patterns of CXCR4 in different colon tissue segments. The expression levels of CXCR4 mRNA and protein in the aganglionic segments were decreased compared to the normal ganglionic and oligoganglionic colon segments (p<0.01). Immunohistochemical staining showed that intensive CXCR4 staining was detected in the ganglion cells and the supporting glial cells in the ganglion in control colon specimens and normal ganglionic and oligoganglionic colon segments from the HSCR patients; however, CXCR4 staining was significantly decreased in the aganglionic colon segments. Immunofluorescence staining showed that CXCR4 staining was mainly detected in the ganglia where RET-positive ganglion cells were observed. Elucidating CXCR4 expression patterns in colon segments could be the basis for further investigations of the potential role of CXCR4 in ENS development.
C-X-C 趋化因子受体 4（CXCR4）在广泛的生理和病理过程中发挥着关键作用，包括干细胞的迁移，如神经嵴衍生细胞。先天性巨结肠（HSCR）是一种发育障碍，其特征是肠神经系统（ENS）发育过程中神经嵴衍生细胞（NCDC）的颅尾迁移过早停止，导致缺乏神经节细胞。在这项研究中，通过手术收集了 61 例 HSCR 患者的结肠组织样本，并将其分为无神经节、少神经节和正常神经节段。通过定量实时聚合酶链反应（PCR）、Western 印迹、免疫组织化学和免疫荧光染色分析不同结肠组织段中 CXCR4 的表达水平和模式。与正常神经节和少神经节结肠段相比，无神经节段中 CXCR4 mRNA 和蛋白的表达水平降低（p<0.01）。免疫组织化学染色显示，在对照结肠标本和 HSCR 患者的正常神经节和少神经节结肠段的神经节中，以及神经节支持胶质细胞中，均可检测到强烈的 CXCR4 染色；然而，在无神经节结肠段中，CXCR4 染色明显减少。免疫荧光染色显示，CXCR4 染色主要在 RET 阳性神经节细胞观察到的神经节中检测到。阐明结肠段中 CXCR4 的表达模式可能是进一步研究 CXCR4 在 ENS 发育中潜在作用的基础。
