Inflammation Sciences Research Group and Manchester Academic Health Science Centre, University of Manchester, Manchester, M13 9PL, UK.
J Crohns Colitis. 2012 Oct;6(9):871-80. doi: 10.1016/j.crohns.2012.01.013. Epub 2012 Mar 3.
Enteroendocrine cells sense gut luminal contents, and orchestrate digestive physiology whilst contributing to mucosal homeostasis and innate immunity. The terminal ileum is the key site of EEC expression but detailed assessment of their subtypes, lineage transcription factors and expression products has not been undertaken in terminal ileal Crohn's disease. Recent Crohn's disease gene wide association studies have linked the neuroendocrine transcription factor Phox2b; while autoantibodies to an enteroendocrine protein, ubiquitination protein 4a, have been identified as a disease behaviour biomarker.
Terminal ileal tissue from small or large bowel Crohn's disease and normal controls was analysed for enteroendocrine marker expression by immunohistochemistry and quantitative polymerase chain reaction. Inflammation was graded by endoscopic, clinical, histological and biochemical scoring.
In small bowel disease, glucagon-like peptide 1 and chromogranin A cells were increased 2.5-fold (p=0.049) and 2-fold (p=0.031) respectively. Polypeptide YY cells were unchanged. Ileal enteroendocrine cell expression was unaffected in the presence of Crohn's colitis. Phox2b was co-localised to enteroendocrine cells and showed a 1.5-fold increase in ileal disease. Significant mRNA increases were noted for chromogranin A (3.3-fold; p=0.009), glucagon-like peptide 1 (3.1-fold; p=0.007) and ubiquitination protein 4a (2.2-fold; p=0.02). Neurogenin 3, an enteroendocrine transcription factor showed ~2 fold-upregulation (p=0.048).
Enhanced enteroendocrine cell activity is present in small bowel disease, and observed in restricted cell lineages. This may impact on the epithelial immune response, cellular homeostasis and nutrient handling and influence appetite via increased satiety signalling in the gut-brain axis.
肠内分泌细胞感知肠道腔内容物，并协调消化生理，同时有助于黏膜稳态和先天免疫。回肠末端是肠内分泌细胞表达的关键部位，但在回肠末端克罗恩病中，尚未对其亚型、谱系转录因子和表达产物进行详细评估。最近的克罗恩病基因广泛关联研究将神经内分泌转录因子 Phox2b 联系在一起；而针对肠内分泌蛋白泛素蛋白 4a 的自身抗体已被确定为疾病行为生物标志物。
通过免疫组织化学和定量聚合酶链反应分析小肠或大肠克罗恩病和正常对照的末端回肠组织中肠内分泌标记物的表达。通过内镜、临床、组织学和生化评分来评估炎症。
在小肠疾病中，胰高血糖素样肽 1 和嗜铬粒蛋白 A 细胞分别增加了 2.5 倍（p=0.049）和 2 倍（p=0.031）。肠肽 YY 细胞无变化。在存在克罗恩结肠炎的情况下，回肠肠内分泌细胞的表达不受影响。Phox2b 与肠内分泌细胞共定位，并在回肠疾病中增加了 1.5 倍。在回肠疾病中，发现嗜铬粒蛋白 A（3.3 倍；p=0.009）、胰高血糖素样肽 1（3.1 倍；p=0.007）和泛素蛋白 4a（2.2 倍；p=0.02）的 mRNA 显著增加。肠内分泌转录因子神经基因 3 表现出约 2 倍的上调（p=0.048）。
在小肠疾病中存在增强的肠内分泌细胞活性，并且仅观察到特定的细胞谱系。这可能会影响上皮免疫反应、细胞稳态以及营养物质的处理，并通过增加肠道-大脑轴中的饱腹感信号来影响食欲。
