Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Proteomics & Metabolomics Platform, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Hangzhou, China.
Biomed Res Int. 2019 Apr 23;2019:3950628. doi: 10.1155/2019/3950628. eCollection 2019.
Inflammatory bowel disease (IBD) has become a major health challenge worldwide. However, the precise etiological and pathophysiological factors involved in IBD remain unclear. Proteomics can be used for large-scale protein identification analysis. In the current study, using tandem mass tag- (TMT-) based shotgun proteomics, proteomic differences between intestinal tissue from health controls, patients with Crohn's disease (CD), and patients with ulcerative colitis (UC) were compared. Proteins with fold change >2 or <0.5 and P value < 0.05 between groups were considered differentially expressed. ProteinAtlas was used to analyze the tissue specificity of differentially expressed proteins (DEPs). Reactome pathway analysis was applied to cluster functional pathways. A total of 4786 proteins were identified, with 59 proteins showing higher levels and 43 showing lower levels in patients with IBD than in controls. Seventeen proteins, including angiotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme 1 (ACE), showed higher levels in CD than in UC. Several novel proteins such as CD38, chitinase 3-like 1 (CHI3L1), olfactomedin 4 (OLFM4), and intelectin 1 were screened out between patients with IBD and controls. When proteins with fold change >1.2 or <0.84 and P value < 0.05 between groups were considered differentially expressed, the expression of 10 proteins, including CD38, involved in the nicotinamide adenine dinucleotide (NAD) metabolism and signaling pathway showed significant changes in IBD. Using the NCBI GEO database, we confirmed increased CD38 mRNA expression in patients with UC and in mouse colitis models. Protein CD38 expression was higher in CD and UC than in normal controls. CD38 expression was higher in inflamed tissues than in noninflamed tissues, and CD38 was located in F4/80-positive cells. Our study may provide novel insights into the molecular pathogenesis of IBD. Further studies are required on the role of NAD metabolism and CD38 in intestinal inflammation.
炎症性肠病（IBD）已成为全球范围内的主要健康挑战。然而，IBD 的确切病因和病理生理因素仍不清楚。蛋白质组学可用于大规模蛋白质鉴定分析。在本研究中，我们使用串联质量标签（TMT）基于 shotgun 蛋白质组学比较了健康对照、克罗恩病（CD）患者和溃疡性结肠炎（UC）患者的肠组织之间的蛋白质组差异。组间 fold change >2 或 <0.5 且 P 值 < 0.05 的蛋白质被认为差异表达。使用 ProteinAtlas 分析差异表达蛋白（DEPs）的组织特异性。应用 Reactome 途径分析对功能途径进行聚类。共鉴定出 4786 种蛋白质，其中 59 种在 IBD 患者中的水平高于对照组，43 种低于对照组。在 CD 患者中，包括血管紧张素转换酶 2（ACE2）和血管紧张素转换酶 1（ACE）在内的 17 种蛋白质的水平高于 UC 患者。在 IBD 患者和对照组之间筛选出几种新型蛋白质，如 CD38、几丁质酶 3 样 1（CHI3L1）、嗅觉素 4（OLFM4）和整合素 1。当组间 fold change >1.2 或 <0.84 且 P 值 < 0.05 的蛋白质被认为差异表达时，包括 CD38 在内的 10 种参与烟酰胺腺嘌呤二核苷酸（NAD）代谢和信号通路的蛋白质的表达在 IBD 中发生显著变化。使用 NCBI GEO 数据库，我们证实了 UC 患者和小鼠结肠炎模型中 CD38 mRNA 表达增加。CD38 在 CD 和 UC 中的表达高于正常对照组。CD38 在炎症组织中的表达高于非炎症组织，并且 CD38 位于 F4/80 阳性细胞中。我们的研究可能为 IBD 的分子发病机制提供新的见解。需要进一步研究 NAD 代谢和 CD38 在肠道炎症中的作用。
