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升高的WTAP通过增加炎症性疾病模型中的m6A修饰来促进高炎症
Yong Ge1,2, Rong Chen1,2, Tao Ling1,2
1Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.
The Journal of clinical investigation
|July 15, 2024
概括
在炎症中高的N6-甲基氨酸 (m6A) 水平与威尔姆斯瘤1-关联蛋白 (WTAP) 有关. 针对 WTAP 的目标
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 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:
- N6-甲基氨酸 (m6A) 修饰失调与炎症性疾病有关.
- 将m6A与炎症联系在一起的精确机制需要进一步阐明.
研究的目的:
- 研究威尔姆斯瘤1-关联蛋白 (WTAP) 在超炎症状态期间m6A修饰中的作用.
- 探索针对炎症性疾病中WTAP介导的m6A沉积的治疗潜力.
主要方法:
- 在超炎症条件下研究了p65对WTAP的转录调节.
- 分析了WTAP过度表达对m6A水平和炎症反应的影响.
- 利用骨髓细胞特异性WTAP缺陷模型来评估其在败血症和炎症性肠病 (IBD) 中的作用.
主要成果:
- 通过p65转录调节WTAP,导致高炎症的m6A水平增加.
- 升级的WTAP通过m6A编写复合物的相分离和聚合促进m6A沉积在炎症转录上.
- 骨髓体WTAP缺乏改善了LPS诱导的败血症和DSS诱导的IBD严重程度.
结论:
- 由WTAP驱动的m6A修饰会加剧促炎反应.
- 针对WTAP阶段分离来降低全球m6A水平是一个有前途的治疗策略.
- 在炎症中WTAP的作用突出了炎症性疾病的一般风险增加机制.
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