Silica-induced initiation of circular ZC3H4 RNA/ZC3H4 pathway promotes the pulmonary macrophage activation
Silica-induced initiation of circular ZC3H4 RNA/ZC3H4 pathway promotes the pulmonary macrophage activation
复制标题
二氧化硅诱导环状 ZC3H4 RNA/ZC3H4 通路的启动促进肺巨噬细胞活化
DOI：
10.1096/fj.201701118r
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发表时间：
2018-06-01
期刊：
影响因子：
4.8
通讯作者：
Chao, Jie
中科院分区：
文献类型：
--
作者：
Yang, Xiyue;Wang, Jing;Chao, Jie
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）是哺乳动物细胞内存在的非编码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。为了阐明这些RNA在SiO2诱导的肺巨噬细胞炎症中的作用，我们研究了circRNA对细胞凋亡、增殖和迁移的上游分子机制和功能作用。采用健康人、患者肺泡巨噬细胞原代培养物和RAW264.7巨噬细胞系，探讨circZC 3 H4 RNA在巨噬细胞活化中的作用。实验结果表明：1）SiO2同时增加circZC 3 H4 RNA表达和增加ZC 3 H4蛋白水平; 2）环形ZC 3 H4（circZC 3 H4）RNA和ZC 3 H4蛋白参与SiO2诱导的巨噬细胞活化; 3）SiO2激活的巨噬细胞通过circZC 3 H4 RNA/ZC 3 H4途径促进成纤维细胞增殖和迁移。在矽肺患者的组织样本中证实了ZC 3 H4蛋白的上调。我们的研究阐明了SiO2诱导的巨噬细胞活化和circZC 3 H4 RNA/ZC 3 H4途径之间的联系，从而为ZC 3 H4的潜在用途提供了新的见解，以开发新的矽肺治疗策略。
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 noncoding RNAs that are present within mammalian cells; however, researchers have not determined whether circRNAs are involved in the pathophysiologic process of silicosis. To elucidate the role of these RNAs in SiO2 induced inflammation in pulmonary macrophages, we investigated the upstream molecular mechanisms and functional effects of circRNAs on cell apoptosis, proliferation, and migration. Primary cultures of alveolar macrophages from healthy donors and from patients and the RAW264.7 macrophage cell line were used to explore the functions of circZC3H4 RNA in macrophage activation. The experimental results indicated the following: 1) SiO2 concomitantly increased circZC3H4 RNA expression and increased ZC3H4 protein levels; 2) circular ZC3H4 (circZC3H4) RNA and ZC3H4 protein participated in SiO2 -induced macrophage activation; and 3) SiO2-activated macrophages promoted fibroblast proliferation and migration via the circZC3H4 RNA/ZC3H4 pathway. The up-regulation of the ZC3H4 protein was confirmed in tissue samples from patients with silicosis. Our study elucidates a link between SiO2 -induced macrophage activation and the circZC3H4 RNA/ZC3H4 pathway, thereby providing novel insight into the potential use of ZC3H4 to develop novel therapeutic strategies for silicosis.