在巨细胞中,PER2/P65驱动的糖原合成酶1转录调节肠道炎症和直肠的发病
Zhao Ding1, Wenhao Ge1, Xiaodong Xu1
1Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China.
The Journal of biological chemistry
|September 3, 2023
概括
节律基因Period2 (Per2) 对于肠道免疫防御至关重要. 它的缺乏导致直肠和炎症,通过损害巨细胞病原体清除.
科学领域:
- 免疫学 免疫学 免疫学
- 时间生物学 时间生物学
- 胃肠病学 胃肠病学
背景情况:
- 炎症性肠病 (IBD) 涉及肠道中的异常免疫反应.
- 生物钟影响免疫防御,但其在肠道炎症中的作用尚不清楚.
研究的目的:
- 调查节律基因Period2 (Per2) 在直肠炎症和失落病原发生中的作用.
- 阐明将Per2与肠道炎症联系起来的分子机制.
主要方法:
- 利用患有Per2缺乏症的小鼠模型研究肠道炎症和直肠倒退.
- 研究了巨细胞中Per2,NF-κB p65和糖原合成酶1 (Gys1) 之间的相互作用.
- 分析了Per2抑制对Gys1水平,糖原合成,病原体清除和肠道微生物群组成的影响.
主要成果:
- 在小鼠中,Per2缺乏导致肠道炎症和自发性直肠脱落的易感性增加.
- PER2直接与NF-κB p65相互作用,调节Gys1的转录.
- 抑制Per2降低了Gys1水平和巨细胞中的糖原合成,损害了病原体清除并改变了肠道微生物的组成.
结论:
- 在调节巨细胞病原体清除和控制肠道炎症方面,Per2起着至关重要的作用.
- 研究结果表明,Per2是与IBD相关的直肠脱落的潜在治疗标.
- 这项研究提出了一种新型的小鼠模型,可以很好地模仿人类直肠.
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