中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (3): 525-531.doi: 10.4103/1673-5374.245478

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

周围神经损伤诱导miR-3099升高可促进许旺细胞的增殖和迁移

  

  • 出版日期:2019-03-15 发布日期:2019-03-15
  • 基金资助:

    本研究由江苏省研究生研究与实践创新项目资助(KYCX17-1910);以及中国江苏高等教育机构优先学术项目(PAPD)资助的项目

Increased levels of miR-3099 induced by peripheral nerve injury promote Schwann cell proliferation and migration

Qian-Yan Liu 1, Yang Miao 2, Xing-Hui Wang 1 , Pan Wang 1 , Zhang-Chun Cheng 1 , Tian-Mei Qian 1   

  1. 1 Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
    2 Department of Pharmacy, Yancheng City No. 1 People’s Hospital, Yancheng, Jiangsu Province, China
  • Online:2019-03-15 Published:2019-03-15
  • Contact: Tian-Mei Qian, qiantm86@ntu.edu.cn.
  • Supported by:

    This study was supported by the Postgraduate Research & Practice Innovation Program of Jiangsu Province of China, No. KYCX17-1910 (to QYL); and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions of China ( PAPD).

摘要:

研究表明,许旺细胞表型可受到microRNAs(miRNAs)的调节。课题组前期研究结果发现并鉴定,在大鼠坐骨神经节段中存在包括miR-3099在内的大量新的miRNA。(1)为了观察周围神经损伤后的miR-3099表达变化,实验采用中国南通大学实验动物中心提供的雄性成年SD大鼠建立了坐骨神经挤压伤大鼠模型;(2)采用实时RT-PCR法检测大鼠坐骨神经损伤后0,1,4,7,14 d压伤段中miR-3099的表达水平发现,与Solexa测序结果一致,损伤坐骨神经组织miR-3099表达上调;(3)采用EdU和Tranwell小室实验观察miR-3099对许旺细胞增殖及迁移的影响发现,miR-3099的表达上调可促进许旺细胞的增殖和迁移,而减少miR-3099的表达抑制上述变化;(4)利用生物信息学工具和高通量方法对miR-3099潜在靶基因进行检测发现,miR-3099可能通过靶向Aqp4,St8sia2,Tnfsf15,Zbtb16,从而影响许旺细胞的增殖和迁移;(5)实验成功检测了周围神经损伤后不同时间点miR-3099的表达变化,证实了周围神经损伤诱导的miR-3099升高,可促进许旺细胞的增殖和迁移。

orcid: 0000-0002-2179-1206(Tian-Mei Qian)

关键词: 周围神经损伤, miR-3099, 坐骨神经, 基因表达, 许旺细胞, 增殖, 迁移, 靶基因, 机制, 神经再生

Abstract:

MicroRNAs (miRNAs) can regulate the modulation of the phenotype of Schwann cells. Numerous novel miRNAs have been discovered and identified in rat sciatic nerve segments, including miR-3099. In the current study, miR-3099 expression levels following peripheral nerve injury were measured in the proximal stumps of rat sciatic nerves after surgical crush. Real-time reverse transcription-polymerase chain reaction was used to determine miR-3099 expression in the crushed nerve segment at 0, 1, 4, 7, and 14 days post sciatic nerve injury, which was consistent with Solexa sequencing outcomes. Expression of miR-3099 was up-regulated following peripheral nerve injury. EdU and tran¬swell chamber assays were used to observe the effect of miR-3099 on Schwann cell proliferation and migration. The results showed that increased miR-3099 expression promoted the proliferation and migration of Schwann cells. However, reduced miR-3099 expression sup¬pressed the proliferation and migration of Schwann cells. The potential target genes of miR-3099 were also investigated by bioinformatic tools and high-throughput outcomes. miR-3099 targets genes Aqp4, St8sia2, Tnfsf15, and Zbtb16 and affects the proliferation and mi¬gration of Schwann cells. This study examined the levels of miR-3099 at different time points following peripheral nerve injury. Our results confirmed that increased miR-3099 level induced by peripheral nerve injury can promote the proliferation and migration of Schwann cells.

Key words: nerve regeneration, peripheral nerve injury, miR-3099, sciatic nerve, gene expression, Schwann cells, proliferation, migration, target genes, mechanisms, neural regeneration