Laboratory of Translational Gastroenterology, GIGA Institute, University of Liège, Liège, Belgium.
Department of Anatomy and Pathology, GIGA Institute, Liège University Hospital CHU, Liège, Belgium.
J Crohns Colitis. 2020 Feb 10;14(2):205-215. doi: 10.1093/ecco-jcc/jjz130.
Based on genetics and natural history, Crohn's disease can be separated into two entities, an ileal and a colonic disease. Protein-based approaches are needed to elucidate whether such subphenotypes are related to distinct pathophysiological processes.
The proteome of ulcer edges was compared with that of paired control tissue samples [n = 32 biopsies] by differential proteomics in the ileum and the colon of Crohn's disease patients [n = 16]. The results were analysed using a hypothesis-driven approach [based on the literature] and a hypothesis-free approach [pathway enrichment analyses] to determine common and segment-specific pathophysiological processes associated with ileal and colonic CD ulcer edges. To confirm the involvement of a key pathway highlighted by proteomics, two proteins were also studied by immunochemistry.
In the ileum and the colon, 4428 and 5204 proteins, respectively, were identified and quantified. Ileal and colonic ulcer edges differed in having a distinct distribution of proteins associated with epithelial-mesenchymal transition, neutrophil degranulation, and ribosomes. Ileal and colonic ulcer edges were similarly characterized by an increase in the proteins implicated in the endoplasmic reticulum protein-processing pathway and a decrease in mitochondrial proteins. Immunochemistry confirmed the presence of endoplasmic reticulum stress in the mucosa of ileal and colonic ulcer edges.
This study provides protein-based evidence for partially distinct pathophysiological processes being associated with ileal and colonic ulcer edges in Crohn's disease patients. This could constitute a first step toward the development of gut segment-specific diagnostic markers and therapeutics.
基于遗传学和自然史，克罗恩病可分为两个实体，即回肠疾病和结肠疾病。需要基于蛋白质的方法来阐明这些亚表型是否与不同的病理生理过程相关。
通过对克罗恩病患者的回肠和结肠的[n=32 个活检样本]进行差异蛋白质组学比较，比较溃疡边缘的蛋白质组与配对的对照组织样本的蛋白质组。使用基于假说的方法[基于文献]和无假说的方法[途径富集分析]来分析结果，以确定与回肠和结肠 CD 溃疡边缘相关的共同和节段特异性病理生理过程。为了确认蛋白质组学突出的关键途径的参与，还通过免疫化学研究了两种蛋白质。
在回肠和结肠中，分别鉴定和定量了 4428 和 5204 种蛋白质。回肠和结肠的溃疡边缘在与上皮-间充质转化、中性粒细胞脱颗粒和核糖体相关的蛋白质分布上存在明显差异。回肠和结肠的溃疡边缘同样以涉及内质网蛋白加工途径的蛋白质增加和线粒体蛋白质减少为特征。免疫化学证实了回肠和结肠溃疡边缘的粘膜中存在内质网应激。
本研究为基于蛋白质的证据提供了支持，即部分不同的病理生理过程与克罗恩病患者的回肠和结肠溃疡边缘相关。这可能是开发肠道节段特异性诊断标志物和治疗方法的第一步。
