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ATF5激活LPAR5,以增强巨细胞的炎症反应,从而加剧类风湿性关节炎的恶化
Caijie Liu1, Yingnan Guo1, Yanni Dong1
1Department of Ultrasound, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, PR China.
lysophosphatidic 酸受体5 (LPAR5) 通过ATF5/LPAR5/PI3K/AKT通路扩大亲炎性巨细胞反应,促进类风湿性关节炎 (RA). 针对这种级联可能会提供新的RA疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 类风湿病学 类风湿病学
背景情况:
- 巨细胞 (Mφ) 在类风湿性关节炎 (RA) 通过表型两极化病原发生过程中至关重要.
- 莱索酸受体5 (LPAR5) 在RA相关Mφ中的作用尚不清楚.
研究的目的:
- 研究LPAR5在调节风湿性关节炎中Mφ的功能作用.
- 阐明RA中LPAR5失调背后的分子机制.
主要方法:
- 从RA患者的突Mφ中对LPAR5表达的分析.
- 在原相关病毒介导的LPAR5在Mφ中的敲击,在原诱导的关节炎小鼠模型中.
- 调查PI3K/AKT信号通路和激活转录因子5 (ATF5) 的参与.
主要成果:
- 在RA突Mφ中LPAR5表达升高,与疾病严重程度相关.
- 通过阻断PI3K/AKT信号传递,LPAR5 Knockdown通过阻断PI3K/AKT信号传递来抑制促炎Mφ极化.
- 一个涉及ATF5,LPAR5和PI3K/AKT信号的积极反循环放大了Mφ的炎症反应.
结论:
- 在RA中,ATF5/LPAR5/PI3K/AKT信号通路是促炎Mφ反应的关键放大器.
- 准这种信号级联为RA治疗提供了潜在的治疗策略.
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