Department of Orthopedic Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Anesthesiology, Changzheng Hospital, The Second Military Medical University, Shanghai, China.
Acta Biochim Biophys Sin (Shanghai). 2019 Dec 13;51(12):1198-1207. doi: 10.1093/abbs/gmz118.
Schwann cells are the main force in spontaneous regeneration after peripheral nerve injury. The neurotrophic factors could promote the regeneration, but clinical applications of these factors are limited by some constraints. Hence, searching for new substances to elevate the function of Schwann cells and facilitate the regeneration of nerve is urgently needed. Syringic acid (SA) is a natural product with neuroprotective activity in vivo, but the role of SA on Schwann cells remains unclear. In this study, we for the first time found that SA was able to promote the proliferation and migration of Schwann cells, two important abilities in the process of regeneration. Then, microRNA (miRNA) microarray analysis was performed and 26 differentially expressed miRNAs (22 down-regulated and 4 up-regulated) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses found that the target genes of these miRNAs were mainly enriched in cellular response to chemical stimulus and cancer-related pathways, respectively. Subsequently, the levels of top 6 down-regulated miRNAs were validated by RT-qPCR and miR-451-5p was shown to be the most down-regulated one. Further experiments demonstrated that inhibition of miR-451-5p significantly promoted the proliferation and migration of Schwann cells. These results suggested that SA promoted the proliferation and migration of Schwann cells via down-regulation of miR-451-5p, and SA could be developed into a promising nutritional supplement to assist peripheral nerve regeneration.
许旺细胞是周围神经损伤后自发再生的主要力量。神经营养因子可以促进再生，但这些因子的临床应用受到一些限制。因此，迫切需要寻找新的物质来提高许旺细胞的功能并促进神经再生。丁香酸（SA）是一种具有体内神经保护活性的天然产物，但 SA 对许旺细胞的作用尚不清楚。在这项研究中，我们首次发现 SA 能够促进许旺细胞的增殖和迁移，这是再生过程中的两个重要能力。然后，进行了 microRNA（miRNA）微阵列分析，鉴定出 26 个差异表达的 miRNA（22 个下调和 4 个上调）。基因本体论（GO）和京都基因与基因组百科全书（KEGG）信号通路分析发现，这些 miRNA 的靶基因主要富集在细胞对化学刺激的反应和癌症相关途径中。随后，通过 RT-qPCR 验证了前 6 个下调 miRNA 的水平，结果表明 miR-451-5p 下调最明显。进一步的实验表明，抑制 miR-451-5p 显著促进了许旺细胞的增殖和迁移。这些结果表明，SA 通过下调 miR-451-5p 促进许旺细胞的增殖和迁移，SA 可以开发成为一种有前途的营养补充剂，以辅助周围神经再生。
