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在患有活性类风湿性关节炎的患者中,TNFAIP3参与炎症的METTL14介导的m6A修饰
Jifeng Tang1, Ziqing Yu2, Jinfang Xia3
1Department of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China and Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Arthritis & rheumatology (Hoboken, N.J.)
|June 16, 2023
概括
在类风湿性关节炎 (RA) 患者中,N6-甲基氨酸 (m6A) 水平和m6A编写器METTL14的水平下降. 针对m6A修饰可能为RA管理提供新的治疗策略.
科学领域:
- 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.
- 分子生物学分子生物学
背景情况:
- 类风湿性关节炎 (RA) 是一种慢性自身免疫性疾病,其特征是关节炎症.
- N6-甲基氨酸 (m6A) 是最常见的内部mRNA修饰,在各种生物过程中起着至关重要的作用.
- 在RA病变发生过程中m6A修饰的作用仍然不完全理解.
研究的目的:
- 调查m6A修饰在类风湿性关节炎 (RA) 进展中的作用.
- 探索甲基转移酶样14 (METTL14) 在RA相关炎症中的功能.
主要方法:
- 来自RA患者和健康对照组的外周血液单核细胞 (PBMC) 用PCR,西斑和ELISA分析了m6A水平和相关蛋白质.
- 使用MeRIP测序和RNA免疫沉降试验评估了甲基转移酶样14 (METTL14) 功能.
- 在体内研究中使用了原抗体诱导性关节炎 (CAIA) 的小鼠模型.
主要成果:
- 在活跃的RA患者的PBMC中,m6A水平和METTL14表达减少,与疾病活性负相关 (DAS28).
- 通过增加PBMCs和CAIA小鼠中的IL-6和IL-17分泌,METTL14敲除会加剧RA炎症.
- 发现m6A修饰通过影响mRNA稳定性和转位来调节TNFAIP3的表达,这是NF-κB通路的关键抑制剂.
结论:
- m6A修饰在RA进展期间调节炎症方面发挥着关键作用.
- METTL14是RA相关炎症的关键调节者.
- 针对m6A修饰呈现出一种潜在的新型治疗策略,用于管理RA.
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