Emergency Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Hubei Clinical Research Center for Emergency and Resuscitation, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Int J Med Sci. 2020 Feb 4;17(4):437-448. doi: 10.7150/ijms.39667. eCollection 2020.
Traumatic brain injury (TBI) is a widespread central nervous system (CNS) condition and a leading cause of death, disability, and long-term disability including seizures and emotional and behavioral issues. To date, applicable diagnostic biomarkers have not been elucidated. MicroRNAs (miRNAs) are enriched and stable in exosomes in plasma. Therefore, we speculated that miRNAs in plasma exosomes might serve as novel biomarkers for TBI diagnosis and are also involved in the pathogenesis of TBI. In this study, we first isolated exosomes from peripheral blood plasma in rats with TBI and then investigated the alterations in miRNA expression in exosomes by high-throughput RNA sequencing. As a result, we identified 50 significantly differentially expressed miRNAs, including 31 upregulated and 19 downregulated miRNAs. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the most highly correlated pathways that were identified were the MAPK signaling pathway, regulation of actin cytoskeleton, Rap1 signaling pathway and Ras signaling pathway. This study provides novel perspectives on miRNAs in peripheral blood plasma exosomes, which not only could be used as biomarkers of TBI diagnosis but could also be manipulated as therapeutic targets of TBI.
创伤性脑损伤（TBI）是一种广泛存在的中枢神经系统（CNS）疾病，也是导致死亡、残疾和长期残疾的主要原因，包括癫痫发作和情绪及行为问题。迄今为止，尚未阐明适用的诊断生物标志物。微小 RNA（miRNA）在血浆外泌体中丰富且稳定。因此，我们推测血浆外泌体中的 miRNA 可能作为 TBI 诊断的新型生物标志物，并且也参与 TBI 的发病机制。在这项研究中，我们首先从 TBI 大鼠的外周血血浆中分离出外泌体，然后通过高通量 RNA 测序研究外泌体中 miRNA 表达的变化。结果，我们鉴定出 50 个显著差异表达的 miRNA，包括 31 个上调和 19 个下调的 miRNA。然后，基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析显示，鉴定出的最相关通路是 MAPK 信号通路、肌动蛋白细胞骨架的调节、Rap1 信号通路和 Ras 信号通路。本研究为外周血血浆外泌体中的 miRNA 提供了新的视角，它们不仅可以作为 TBI 诊断的生物标志物，还可以作为 TBI 的治疗靶点。
