circIFNGR2通过巨细胞极化调节结性脊髓炎相关的炎症
Minkai Song1, Xiangyu Wang2, Jiawen Gao3
1Division of Orthopaedic Surgery, Department of Orthopaedics, NanFang Hospital, Southern Medical University, Guangzhou, China.
iScience
|July 31, 2023
概括
像circIFNGR2这样的循环RNAs (circRNAs) 通过激活巨细胞来促进结性脊髓炎 (AS). 抑制cirCIFNGR2可能通过减少炎症来为AS提供治疗策略.
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:
- 巨细胞在类风湿性疾病中发挥关键作用,例如结性脊髓炎 (AS).
- 循环RNAs (circRNAs) 与自身免疫性疾病炎症有关,但它们在AS中的作用尚不清楚.
研究的目的:
- 调查circIFNGR2在AS病变发生中的作用.
- 阐明circIFNGR2通过哪些分子机制影响AS中的巨细胞激活和炎症.
主要方法:
- 从AS患者的外周血液单核细胞中量化cirCIFNGR2表达.
- 进行了体外测试,以评估circIFNGR2对巨细胞增殖,极化 (M1/M2) 和信号通路 (NF-κB/Akt) 的影响.
- 研究了circIFNGR2,miR-939和RNA结合蛋白eIF4A3.3.之间的相互作用.
- 评估了miR-939的治疗潜力和circIFNGR2在原诱导关节炎小鼠模型中的作用.
主要成果:
- 在AS患者中,cirCIFNGR2表达升高,与疾病严重程度相关.
- 循环IFNGR2增强了巨细胞的增殖,促进了M1两极分化 (通过iNOS/TNFα),并通过海绵化miR-939.3抑制了M2两极分化.
- eIF4A3被确定为circIFNGR2生产的积极调节者.
- miR-939在体内显示出对关节损伤的保护作用,而circIFNGR2.2可以逆转这些保护作用.
结论:
- eIF4A3诱导的circiFNGR2通过miR-939通路驱动巨细胞相关的炎症,促进AS的发病.
- circIFNGR2代表了一种潜在的治疗点,用于控制结性脊柱炎的炎症.
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