维生素A缺乏会触发结肠甲基化,通过降低SGK1/FOXO通路的调节,可能会损害结肠神经元
Bei Tong1, Junyan Yan1, Zhujun Sun1
1Children Nutrition Research Center Children's Hospital of Chongqing Medical University Chongqing Key Laboratory of Child Neurodevelopmental and Cognitive Disorders Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and Disorders Chongqing China.
维生素A缺乏 (VAD) 会导致结肠中的DNA高甲基化,延迟胃肠道的传输. 补充维生素A (VA) 可以减轻这些影响,这表明VAD,甲基化和肠道功能之间存在联系.
科学领域:
- 胃肠病学 胃肠病学
- 神经科学是一个神经科学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- DNA甲基化影响肠道功能,但其在维生素A缺乏 (VAD) 期间在肠道神经系统中的作用尚不清楚.
- 维生素A对于正常的发育和功能至关重要.
研究的目的:
- 研究VAD对肠道神经系统内DNA甲基化的影响.
- 阐明连接VAD,DNA甲基化和结肠功能障碍的分子机制.
主要方法:
- 在VAD和正常维生素A (VAN) 之间的胃肠道过境时间的比较.
- RNA测序和DNA甲基组分析 (减少二硫酸盐测序).
- 验证DNA甲基转移酶表达和基因甲基化水平.
主要成果:
- VAD显著延迟了胃肠道过渡时间,并增加了DNA甲基转移酶表达 (DNMT1,DNMT3a,DNMT3b).
- VAD导致大肠促销物和前体中广泛的DNA高甲基化,特别是在*Sgk1*基因中.
- 在VAD大鼠中观察到结肠神经元形态受损和SGK1/FOXO信号活动减少.
- 补充维生素A可以逆转VAD引起的变化.
结论:
- 维生素A缺乏导致结肠高甲基化,可能会降低SGK1/FOXO通路的调节,并导致结肠过境功能障碍.
- 产后早期的维生素A补充可以改善VAD诱导的结肠内表观遗传和功能缺陷.
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