circRNA Mediates Silica-Induced Macrophage Activation Via HECTD1/ZC3H12A-Dependent Ubiquitination.
circRNA Mediates Silica-Induced Macrophage Activation Via HECTD1/ZC3H12A-Dependent Ubiquitination.
复制标题
circRNA 通过 HECTD1/ZC3H12A 依赖性泛素化介导二氧化硅诱导的巨噬细胞激活。
作者：
Zhou Z;Jiang R;Yang X;Guo H;Fang S;Zhang Y;Cheng Y;Wang J;Yao H;Chao J
基本原理：二氧化硅（SiO2）吞噬进入肺细胞引起炎症级联反应，导致成纤维细胞增殖和迁移，随后发生纤维化。环状RNA（circRNA）是在哺乳动物细胞中检测到的非编码RNA的一个亚类;然而，研究人员尚未确定circRNA是否参与矽肺的病理生理过程。研究circRNA上游分子机制及其对细胞凋亡、增殖和迁移的功能影响，以阐明circRNA在SiO2诱导的肺巨噬细胞炎症中的作用。研究方法：本研究采用健康人和患者肺泡巨噬细胞原代培养物以及RAW264.7巨噬细胞系，探讨了circHECTD 1（HECT domain E3 ubiquitin protein ligase 1）在巨噬细胞活化中的作用。结果如下：实验结果表明：1）SiO2同时降低circHECTD 1水平并增加HECTD 1蛋白表达; 2）circHECTD 1和HECTD 1通过泛素化参与SiO2诱导的巨噬细胞活化; 3）SiO2活化的巨噬细胞通过circHECTD 1/HECTD 1途径促进成纤维细胞增殖和迁移。来自矽肺患者的组织样品证实了HECTD 1的上调。结论：我们的研究阐明了SiO2诱导的巨噬细胞活化与circHECTD 1/HECTD 1通路之间的联系，从而为HECTD 1在开发治疗矽肺的新治疗策略中的潜在用途提供了新的见解。
Rationale: Phagocytosis of silicon dioxide (SiO2) into lung cells causes an inflammatory cascade that results in fibroblast proliferation and migration, followed by fibrosis. Circular RNAs (circRNAs) are a subclass of non-coding RNAs detected within mammalian cells; however, researchers have not determined whether circRNAs are involved in the pathophysiological process of silicosis. The upstream molecular mechanisms and functional effects on cell apoptosis, proliferation and migration were investigated to elucidate the role of circRNAs in SiO2-induced inflammation in pulmonary macrophages. Methods: Primary cultures of alveolar macrophages from healthy donors and patients as well as the RAW264.7 macrophage cell line were used to explore the functions of circHECTD1 (HECT domain E3 ubiquitin protein ligase 1) in macrophage activation. Results: The results of the experiments indicated that 1) SiO2 concomitantly decreased circHECTD1 levels and increased HECTD1 protein expression; 2) circHECTD1 and HECTD1 were involved in SiO2-induced macrophage activation via ubiquitination; and 3) SiO2-activated macrophages promoted fibroblast proliferation and migration via the circHECTD1/HECTD1 pathway. Tissue samples from silicosis patients confirmed the upregulation of HECTD1. Conclusions: Our study elucidated a link between SiO2-induced macrophage activation and the circHECTD1/HECTD1 pathway, thereby providing new insight into the potential use of HECTD1 in the development of novel therapeutic strategies for treating silicosis.