皮质NSD2维持FMO介导的 taurine生物合成,以防止肠道屏障破坏
Yue Xu1,2, Xiuying Xiao3, Chunxiao Ma1,2
1State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
在炎症性肠病 (IBD) 中降低NSD2水平会损害 taurine 生合成,恶化肠道炎症. 恢复牛素水平可以缓解IBD症状,突出NSD2.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 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:
- 炎症性肠病 (IBD) 的发病过程复杂,并未得到充分理解.
- NSD2是一种基因组甲基转移酶,在IBD肠道上皮细胞 (IECs) 中降低调节.
- 在IBD中NSD2的特定功能尚不清楚.
研究的目的:
- 研究NSD2在维持肠道屏障功能和预防IBD炎症中的作用.
- 阐明NSD2在IBD中的功能背后的分子机制.
主要方法:
- 对临床IBD患者数据和IBD小鼠模型的分析.
- 产生NSD2淘汰赛小鼠和隔离IECs.
- RNA测序,ChIP测序和分子/细胞实验以确定途径和验证机制.
- 救援实验证实了分子机制.
主要成果:
- 在小鼠IEC中NSD2缺陷加剧了表皮质屏障破坏和IBD中的炎症.
- NSD2损失减少了H3K36me2和含有黄素的单氧化酶 (FMO) mRNA,降低了牛生物合成.
- 氨酸补充剂显著缓解了NSD2缺乏引起的IBD的症状.
结论:
- 通过维持FMO介导的 taurine生物合成,NSD2对于预防肠道炎症至关重要.
- NSD2-H3K36me2-taurine生物合成途径对于肠粘膜屏障恒温至关重要.
- 准NSD2介导的 taurine 生物合成可能为IBD提供治疗策略.
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