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在FTO介导的RNAm6中,甲基化调节了类风湿性关节炎中的突侵略和炎症
Ruiru Li1, Yu Kuang1, Yuanyuan Niu2
1Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
脂肪质量和与肥胖相关的蛋白质 (FTO) 通过调节N6-甲基氨酸 (m6A) 修饰,驱动类风湿性关节炎 (RA) 炎症和关节损伤. 抑制FTO可以降低RA的严重程度,这表明FTO是潜在的治疗标.
科学领域:
- 类风湿病学 类风湿病学
- 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:
- 纤维细胞样突细胞 (FLS) 是肌炎和类风湿性关节炎 (RA) 关节损伤的关键驱动因素.
- N6-甲基氨酸 (m6A) 是一种普遍存在的mRNA修饰,与各种疾病有关,但其在RA病原发生中的作用尚不清楚.
研究的目的:
- 为了研究m6A脱甲基酶脂肪质量和与肥胖相关的蛋白质 (FTO) 在类风湿性关节炎中的作用.
主要方法:
- 在RA患者的FLS和synovium中评估FTO表达.
- 在RA FLS模型中使用了FTO敲击和FTO抑制剂FB23-2.
- 研究了FTO对ADAMTS15mRNA稳定性和IGF2BP1相互作用的影响.
- 在原诱导性关节炎 (CIA) 的小鼠和老鼠模型中评估治疗疗效.
主要成果:
- 在RA FLS和阴膜中,FTO表达升高.
- 抑制FTO可以减少RA FLS的迁移,入侵和炎症反应.
- FTO过度表达增强了RA FLS的迁移,入侵和炎症.
- FTO通过一个m-IGF2BP1依赖机制稳定了ADAMTS15mRNA.
- 在CIA模型中,FB23-2治疗或FTO shRNA注射显著改善了关节炎的严重程度.
结论:
- 通过FTO介导的m6 一种修改对RA的关节炎症和损伤有显著的贡献.
- 阻断FTO是一种有前途的治疗策略,用于治疗类风湿性关节炎.
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