Song Minkai, Wang Xiangyu, Gao Jiawen, Jiang Weizhou, Bi Enguang, An Taixue, Wang Ting, Chen Zishuo, Liu Weilu, Shi Zhanjun, Xiao Jun, Zhang Chao
Division of Orthopaedic Surgery, Department of Orthopaedics, NanFang Hospital, Southern Medical University, Guangzhou, China.
Department of Endocrinology & Metabolism, NanFang Hospital, Southern Medical University, Guangzhou, China.
iScience. 2023 Jul 10;26(8):107325. doi: 10.1016/j.isci.2023.107325. eCollection 2023 Aug 18.
Macrophages activation is crucial in pathogenesis of rheumatic diseases like ankylosing spondylitis (AS). Circular RNAs (circRNAs)-induced macrophage-associated inflammation participates in many autoimmune diseases but remains elusive in AS. Here, we verified increased expression of circIFNGR2 in peripheral blood mononuclear cells from patients with AS and its expression levels were correlated with the AS severity. assays revealed that circIFNGR2 enhances macrophage proliferation, and regulates M1/M2 macrophage polarization and NF-κB/Akt pathways. We identified that circIFNGR2 promoted the expression of iNOS/TNFα and M1 polarization, and restrained M2 polarization by sponging miR-939. Additionally, the RNA-binding protein, eIF4A3, was found to enhance the production of circIFNGR2. Interestingly, miR-939 attenuated joint damage in collagen-induced arthritis mice, whereas circIFNGR2 reversed this effect. Our findings highlight the pro-inflammatory roles of eIF4A3-induced circIFNGR2 in AS by modulating macrophage-associated inflammation through miR-939.
巨噬细胞活化在强直性脊柱炎（AS）等风湿性疾病的发病机制中至关重要。环状RNA（circRNA）诱导的巨噬细胞相关炎症参与多种自身免疫性疾病，但在AS中仍不清楚。在此，我们证实了AS患者外周血单个核细胞中circIFNGR2表达增加，且其表达水平与AS严重程度相关。实验表明，circIFNGR2增强巨噬细胞增殖，并调节M1/M2巨噬细胞极化以及NF-κB/Akt信号通路。我们发现circIFNGR2通过海绵吸附miR-939促进诱导型一氧化氮合酶（iNOS）/肿瘤坏死因子α（TNFα）的表达和M1极化，并抑制M2极化。此外，发现RNA结合蛋白eIF4A3可增强circIFNGR2的产生。有趣的是，miR-939减轻了胶原诱导的关节炎小鼠的关节损伤，而circIFNGR2则逆转了这种作用。我们的研究结果突出了eIF4A3诱导的circIFNGR2通过miR-939调节巨噬细胞相关炎症在AS中的促炎作用。
