溃疡性结肠炎的多组学增强的深层表型鉴定了报告功能性缓解状态的生物标志物特征。

IF 8.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Journal of Crohns & Colitis Pub Date : 2023-10-20 DOI:10.1093/ecco-jcc/jjad052
Lukas Janker, Dina Schuster, Patricia Bortel, Gerhard Hagn, Samuel M Meier-Menches, Thomas Mohr, Johanna C Mader, Astrid Slany, Andrea Bileck, Julia Brunmair, Christian Madl, Lukas Unger, Barbara Hennlich, Barbara Weitmayr, Giorgia Del Favero, Dietmar Pils, Tobias Pukrop, Nikolaus Pfisterer, Thomas Feichtenschlager, Christopher Gerner
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引用次数: 3

摘要

引言:溃疡性结肠炎是一种发病率不断上升、病因不明的慢性疾病。通过多组学分析进行的深层分子表型分析可以为疾病过程和缓解状态的特征提供新的见解。方法:通过对人体组织样本的蛋白质组分析来评估UC的病理机制,这些样本取自研究中12名患者的5个不同结肠位置。通过基于质谱的多组学分析的横断面设置,与健康对照组相比,评估了系统性疾病相关的改变,该分析包括UC患者在急性发作和缓解期间获得的血浆中的蛋白质、代谢物和类二十碳烷。结果:组织蛋白质组分析表明,结肠炎与中性粒细胞、巨噬细胞、B和T细胞、成纤维细胞、内皮细胞和血小板的激活以及缺氧应激有关,并表明线粒体蛋白普遍下调,同时建立了明显的促伤愈合活性,包括瘢痕形成。尽管免疫细胞明显上调了促炎蛋白,但结肠炎相关的上皮细胞、成纤维细胞、内皮细胞和血小板似乎主要参与抗炎和促进伤口愈合的蛋白。血浆蛋白质组学表明慢性炎症和血小板活化,而血浆代谢组学则确定了与疾病相关的肠道和肠道微生物组衍生代谢产物的失调。缓解后,一些(但不是全部)候选分子生物标志物水平恢复正常。结论:研究结果可能表明,微血管损伤和血小板失调在病情缓解时很难解决,但作为疾病相关的分子特征明显持续存在。这项研究将局部和全身分子改变整合到UC病理机制模型中,有可能支持评估UC患者的疾病和缓解状态。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Multiomics-empowered Deep Phenotyping of Ulcerative Colitis Identifies Biomarker Signatures Reporting Functional Remission States.

Introduction: Ulcerative colitis [UC] is a chronic disease with rising incidence and unclear aetiology. Deep molecular phenotyping by multiomics analyses may provide novel insights into disease processes and characteristic features of remission states.

Methods: UC pathomechanisms were assessed by proteome profiling of human tissue specimens, obtained from five distinct colon locations for each of the 12 patients included in the study. Systemic disease-associated alterations were evaluated thanks to a cross-sectional setting of mass spectrometry-based multiomics analyses comprising proteins, metabolites, and eicosanoids of plasma obtained from UC patients during acute episodes and upon remission, in comparison with healthy controls.

Results: Tissue proteome profiling indicated colitis-associated activation of neutrophils, macrophages, B and T cells, fibroblasts, endothelial cells and platelets, and hypoxic stress, and suggested a general downregulation of mitochondrial proteins accompanying the establishment of apparent wound healing-promoting activities including scar formation. Whereas pro-inflammatory proteins were apparently upregulated by immune cells, the colitis-associated epithelial cells, fibroblasts, endothelial cells, and platelets seemed to predominantly contribute anti-inflammatory and wound healing-promoting proteins. Blood plasma proteomics indicated chronic inflammation and platelet activation, whereas plasma metabolomics identified disease-associated deregulations of gut and gut microbiome-derived metabolites. Upon remission several, but not all, molecular candidate biomarker levels recovered back to normal.

Conclusion: The findings may indicate that microvascular damage and platelet deregulation hardly resolve upon remission, but apparently persist as disease-associated molecular signatures. This study presents local and systemic molecular alterations integrated in a model for UC pathomechanisms, potentially supporting the assessment of disease and remission states in UC patients.

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来源期刊
Journal of Crohns & Colitis
Journal of Crohns & Colitis 医学-胃肠肝病学
CiteScore
15.50
自引率
7.50%
发文量
1048
审稿时长
1 months
期刊介绍: Journal of Crohns and Colitis is concerned with the dissemination of knowledge on clinical, basic science and innovative methods related to inflammatory bowel diseases. The journal publishes original articles, review papers, editorials, leading articles, viewpoints, case reports, innovative methods and letters to the editor.
期刊最新文献
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