Wang Jue, Cao Bin, Gao Yan, Chen Yu-Hua, Feng Juan
Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning Province, China.
Neural Regen Res. 2023 Jun;18(6):1316-1320. doi: 10.4103/1673-5374.357901.
LncRNA (long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis. We previously discovered a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke. In this study, we used serum from patients with ischemic stroke, and mouse and cell culture models to elucidate the roles of plasma and neuronal exosomes in the regulatory effect of lncRNA H19 on insulin-like growth factor-1 and its mechanism in ischemic stroke, using western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assays. Plasma exosomal lncRNA H19 was negatively associated with blood levels of insulin-like growth factor-1 in samples from patients with cerebral ischemic stroke. In a mouse model, levels of exosomal lncRNA H19 were positively correlated with plasma and cerebral lncRNA H19. In a cell co-culture model, we confirmed that lncRNA H19 was transported from neurons to astrocytes by exosomes to induce downregulation of insulin-like growth factor-1 through the H19/let-7a/insulin-like growth factor-1 receptor axis. This study provides the first evidence for the transportation of lncRNA H19 by exosomes and the relationship between lncRNA H19 and insulin-like growth factor-1.
长链非编码RNA(LncRNA)H19是H19基因的一种转录本,在胚胎发育过程中表达。我们之前发现环状LncRNA H19在脑缺血性中风的发病和预后中发挥作用。在本研究中,我们使用缺血性中风患者的血清以及小鼠和细胞培养模型,通过蛋白质印迹法、定量实时聚合酶链反应和酶联免疫吸附测定,来阐明血浆和神经元外泌体在LncRNA H19对胰岛素样生长因子-1的调节作用及其在缺血性中风中的机制。在脑缺血性中风患者样本中,血浆外泌体LncRNA H19与胰岛素样生长因子-1的血液水平呈负相关。在小鼠模型中,外泌体LncRNA H19水平与血浆和脑LncRNA H19呈正相关。在细胞共培养模型中,我们证实LncRNA H19通过外泌体从神经元转运至星形胶质细胞,通过H19/let-7a/胰岛素样生长因子-1受体轴诱导胰岛素样生长因子-1下调。本研究首次提供了外泌体转运LncRNA H19以及LncRNA H19与胰岛素样生长因子-1之间关系的证据。