Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 91905, Israel.
Institute of Biochemistry, Food Science and Nutrition, Robert H Smith Faculty of Agriculture, Food and Environment, The Hebrew University, Rehovot 7610001, Israel.
Int J Mol Sci. 2024 Jan 25;25(3):1488. doi: 10.3390/ijms25031488.
Patients with active ulcerative colitis (UC) display a misalignment of the circadian clock, which plays a vital role in various immune functions. Our aim was to characterize the expression of clock and inflammation genes, and their mutual regulatory genes in treatment-naïve pediatric patients with UC. Using the Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) platform and R algorithms, we analyzed rectal biopsy transcriptomic data from two cohorts (206 patients with UC vs. 20 healthy controls from the GSE-109142 study, and 43 patients with UC vs. 55 healthy controls from the GSE-117993 study). We compared gene expression levels and correlation of clock genes (, , , , , ), inflammatory genes (, , , , , ) and their mutual regulatory genes (, , , , , , , ) in patients with active UC and healthy controls. The clock genes , , and and the inflammatory genes , , , , and were significantly upregulated in patients with active UC. The genes encoding the mutual regulators , , , and were significantly downregulated in patients with UC. A uniform pattern of gene expression was found in healthy controls compared to the highly variable expression pattern in patients with UC. Among the healthy controls, inflammatory genes were positively correlated with clock genes and they all showed reduced expression. The difference in gene expression levels was associated with disease severity and endoscopic score but not with histological score. In patients with active UC, clock gene disruption is associated with abnormal mucosal immune response. Disrupted expression of genes encoding clock, inflammation and their mutual regulators together may play a role in active UC.
患有活动期溃疡性结肠炎 (UC) 的患者表现出生物钟的失调，生物钟在各种免疫功能中起着至关重要的作用。我们的目的是描述未经治疗的儿科 UC 患者中时钟和炎症基因及其相互调节基因的表达。我们使用炎症性肠病转录组和元转录组荟萃分析 (IBD TaMMA) 平台和 R 算法，分析了来自两个队列的直肠活检转录组数据（来自 GSE-109142 研究的 206 例 UC 患者与 20 例健康对照者，以及来自 GSE-117993 研究的 43 例 UC 患者与 55 例健康对照者）。我们比较了活动期 UC 患者和健康对照者中时钟基因（,,,, ）、炎症基因（,,,, ）及其相互调节基因（,,,,,, ）的基因表达水平和相关性。在活动期 UC 患者中，时钟基因,,,, 和 以及炎症基因,,,, 和 显著上调。编码相互调节基因,,,,,, 的基因在 UC 患者中显著下调。与 UC 患者高度可变的表达模式相比，健康对照者的基因表达模式较为一致。在健康对照者中，炎症基因与时钟基因呈正相关，且均表现为表达下调。基因表达水平的差异与疾病严重程度和内镜评分相关，但与组织学评分无关。在活动期 UC 患者中，时钟基因的破坏与异常的黏膜免疫反应有关。时钟基因、炎症基因及其相互调节基因表达的紊乱可能共同参与了活动期 UC 的发病机制。
