由于NPY1R基因甲基化的表观遗传调节,UHRF1缺乏会加剧肠道炎症
Yanan Han1,2, Lina Sun1, Yanxing Liu2
1The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
JCI insight
|February 9, 2026
概括
缺乏UHRF1会通过破坏肠道屏障的完整性,使炎症性肠病 (IBD) 恶化. 恢复UHRF1功能或准UHRF1/NPY1R轴可能为IBD提供新的治疗策略.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
背景情况:
- 表观遗传修饰是炎症性肠病 (IBD) 发病的关键.
- 一种DNA甲基化调节剂UHRF1与癌症有关,但其在IBD中的作用尚不清楚.
研究的目的:
- 为了研究UHRF1在IBD病变发生过程中的功能.
- 阐明UHRF1在肠道炎症中的作用背后的分子机制.
主要方法:
- 在IBD患者组织中分析UHRF1水平.
- 使用了人类细胞模型和肠上皮特异性的Uhrf1-KO小鼠模型.
- 研究了UHRF1/NPY1R相互作用及其下游信号通路.
主要成果:
- 在炎症性IBD组织中,UHRF1降低,其缺乏会加剧肠道上皮细胞损伤.
- UHRF1缺乏导致NPY1R上调,减弱cAMP/PKA/CREB信号,并增强NF-κB激活.
- miR-141被确定为NPY1R的负调节剂.
结论:
- UHRF1/NPY1R轴是肠道炎症中的关键表观遗传调节器.
- UHRF1作为IBD进展的关键缓解剂.
- 这一监管轴对IBD诊断和治疗有潜力.
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