在复发性类风湿关节炎中向纤维细胞生长因子10/FGFR1的作用和治疗潜力
Xiaohui Meng1,2,3, Zechuan Chen4, Teng Li4
1Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Arthritis & rheumatology (Hoboken, N.J.)
|August 16, 2023
概括
风湿性关节炎 (RA) 复发中的纤维细胞样同胞细胞 (FLS) 是由纤维细胞生长因子 (FGF) 途径驱动的. 抑制FGF10/FGFR1显示了对活跃的RA的治疗潜力.
科学领域:
- 类风湿病学 类风湿病学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 纤维细胞样同胞细胞 (FLS) 是类风湿性关节炎 (RA) 病原体的关键参与者,有助于炎症和关节破坏.
- 在RA复发和缓解期间FLS的特定作用和异质性尚未完全理解.
- 了解FLS监管可能会揭示疾病修饰性抗风湿药物 (DMARDs) 的新疗法标.
研究的目的:
- 研究RA复发与缓解中的FLS异质性.
- 确定在活跃疾病期间调节FLS的关键信号通路.
- 探索针对RA中已识别的途径的治疗潜力.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 和从复发和缓解的RA患者的突组织的空间转录组学.
- 定量实时PCR (qPCR) 和多重免疫组织化学 (mIHC) 用于途径验证.
- 在体外FLS刺激和体内研究使用原诱导性关节炎 (CIA) 鼠标模型.
主要成果:
- scRNA-seq确定了不同的内和下线FLS子集.
- 纤维细胞生长因子 (FGF) 途径,特别是FGF10,在RA复发期间在外层FLS中显著上调.
- 抑制FGF10降低了关键的炎症媒介,FGF10在体外增强了骨质侵蚀,而抑制FGFR1在CIA的老鼠模型中显示出治疗效果.
结论:
- 在RA复发期间,FGF信号通路对FLS活动至关重要.
- 针对FGF10/FGFR1轴的制是一种有前途的治疗策略,用于管理活跃的RA.
- 这项研究突出了FLS异质性,并确定了开发新型RA治疗的具体途径.
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