中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (6): 1316-1320.doi: 10.4103/1673-5374.357901

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

外泌体介导lncRNA H19调节缺血性脑卒中后胰岛素样生长因子1的表达

  

  • 出版日期:2023-06-15 发布日期:2023-01-05
  • 基金资助:
    国家自然科学基金(82271353)和辽宁省重点研究开发计划(2020JH2/10300047)

Exosome-transported lncRNA H19 regulates insulin-like growth factor-1 via the H19/let-7a/insulin-like growth factor-1 receptor axis in ischemic stroke

Jue Wang1, Bin Cao1, Yan Gao1, Yu-Hua Chen2, Juan Feng1, *   

  1. 1Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China; 2Department 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
  • Online:2023-06-15 Published:2023-01-05
  • Contact: Juan Feng, MD, fengjuan99999@hotmail.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82271353 (to JW), and Key Research and Development Program of Liaoning Province, No. 2020JH2/10300047 (to JF).

摘要:

作者所在课题组既往研究发现长链非编码RNA H19在缺血性脑卒中的发病、进展及预后过程中均发挥重要作用。实验旨在阐明血浆和神经元外泌体在长非编码RNA H19对缺血性脑卒中胰岛素样生长因子1水平的调节作用及其机制。结果显示,血浆外泌体lncRNA H19与脑缺血性脑卒中患者血样中的胰岛素样生长因子1水平呈负相关。动物模型结果显示lncRNA H19是通过外泌体从大脑运输到血液的。细胞共培养模型证实了外泌体将lncRNA H19从神经元运输至星形细胞,通过H19/let-7a/IGF1R轴诱导胰岛素样生长因子1表达的下调。该研究首次描述了外泌体对lncRNA H19的运输以及lncRNA H19和胰岛素样生长因子1之间的关系,开辟了缺血性脑卒中机制研究的新思路,为长链非编码RNA H19作为缺血性脑卒中的治疗新靶点应用于临床提供了实验学依据。

https://orcid.org/0000-0002-8895-4831 (Juan Feng)

Abstract: 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. 

Key words: cerebral ischemia, exosomes, H19, insulin-like growth factor-1, insulin-like growth factor 1 receptor, ischemic stroke, long non-coding RNA