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编码时钟,炎症和它们的相互调节者的粘膜基因在患有活性性结肠炎的儿科患者中被破坏
Sapir Labes1, Oren Froy2, Yuval Tabach1
1Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 91905, Israel.
儿科性结肠炎 (UC) 患者表现出昼夜时间的干扰和炎症基因表达. 这种干扰与疾病的严重程度和肠道内膜异常免疫反应有关.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 时间生物学 时间生物学
背景情况:
- 性结肠炎 (UC) 与昼夜时钟失调有关,影响免疫功能.
- 了解未经治疗的儿科UC中的基因表达对于识别疾病机制至关重要.
研究的目的:
- 描述时钟基因,炎症基因及其相互调节基因的表达在未经治疗的儿童患者中,活跃的UC.
- 调查基因表达模式与UC疾病严重程度之间的相关性.
主要方法:
- 使用IBD TaMMA平台和R算法,分析两组患有UC的儿科患者和健康对照者的直肠活检转录组数据.
- 对钟基因 (BMAL1, CLOCK, PER1, PER2, CRY1, CRY2),炎症基因 (IκB, IL10, NFκB1, NFκB2, IL6, TNFα) 和相互调节剂 (RORα, RORγ, REV-ERBα, PGC1α, PPARα, PPARγ, AMPK, SIRT1) 的基因表达水平和相关性的比较.
主要成果:
- 在活跃的UC患者中,钟基因 (BMAL1,CLOCK,PER1,CRY1) 和炎症基因 (IκB,IL10,NFκB1,NFκB2,IL6,TNFα) 的显著上调.
- 在UC患者中,相互调节基因 (RORα,RORγ,PGC1α,PPARα,PPARγ) 的显著下调.
- 观察到不同的基因表达模式:在健康对照组中均,在UC患者中高度可变;与疾病严重程度和内镜评分相关的基因表达差异.
结论:
- 在活性UC中中断的时钟基因表达与异常的粘膜免疫反应有关.
- 时钟,炎症和调节基因的异常表达可能有助于活跃的UC病变发生.
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