中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (1): 144-151.doi: 10.4103/1673-5374.314114

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

环状RNA circPrkcsh可抑制脊髓损伤后的炎症反应

  

  • 出版日期:2022-01-05 发布日期:2021-09-22

Down-regulating Circular RNA Prkcsh suppresses the inflammatory response after spinal cord injury

Jia-Nan Chen1, Yi-Ning Zhang2, Li-Ge Tian1, Ying Zhang1, Xin-Yu Li1, Bin Ning1, *   

  1. 1Department of Orthopedics, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China; 2Department of Orthopedics, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China
  • Online:2022-01-05 Published:2021-09-22
  • Contact: Bin Ning, MD, ningbin@sdu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81771346, 82071383; the Taishan Scholar Program of Shandong Province of China, No. tsqn201812156; Spring City Leader Talent Support Plan, No. 201984; and Rongxiang Regenerative Medicine Foundation of Shandong University, No. 2019SDRX-23 (all to BN).

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摘要：

环状RNA是一类保守的内源性非编码RNA，主要参与转录和转录后基因调控，且在神经系统中高度富集，可参与调节多种神经细胞的存活与分化，甚至可促进卒中后神经功能的恢复，但是其在脊髓损伤后炎症反应中的作用仍然未知。（1）实验以改良的Allen打击法建立T9脊髓损伤小鼠模型，发现有16013种环状RNA和960种微小RNA在脊髓损伤后存在差异表达，其中circPrkcsh的表达变化最为显著；（2）以肿瘤坏死因子α在体外诱导星形胶质细胞，以模拟脊髓损伤后的炎症反应。发现损伤细胞中circPrkcsh的表达升高，而miR-488表达下降，同时发现还circPrkcsh可调节炎症相关基因Ccl2。在肿瘤坏死因子α诱导的星形胶质细胞中，敲低circPrkcsh可通过上调miR-488降低Ccl2的表达，并减少体外炎性细胞因子的分泌；（3）结果表明，差异表达环状RNA可参与脊髓损伤后的炎症反应，并作为某些微小RNA的调节剂，其中circPrkcsh可作为miR-488的海绵(miRNA sponge)调节Ccl2表达，这可能为脊髓损伤治疗提供新的潜在靶点。实验于2017年3月3日经山东大学动物伦理委员会批准（批准号KYLL-20170303）。

https://orcid.org/0000-0002-7592-9485 (Bin Ning)

关键词: font-family:宋体, ">环状font-family:Calibri, sans-serif, ">RNAfont-family:宋体, ">, 脊髓损伤, 炎症, 非编码font-family:Calibri, sans-serif, ">RNAfont-family:宋体, ">, 竞争性内源font-family:Calibri, sans-serif, ">RNA, miR-488font-family:宋体, ">, font-family:Calibri, sans-serif, "> Prkcshfont-family:宋体, ">, font-family:Calibri, sans-serif, ">Ccl2font-family:宋体, ">, 星形胶质细胞, font-family:Calibri, sans-serif, ">RNAfont-family:宋体, ">测序

Abstract: Circular RNAs (circRNAs) are a class of conserved, endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation and are highly enriched in the nervous system. They participate in the survival and differentiation of multiple nerve cells, and may even promote the recovery of neurological function after stroke. However, their role in the inflammatory response after spinal cord injury remains unclear. In the present study, we established a mouse model of T9 spinal cord injury using the modified Allen’s impact method, and identified 16,013 circRNAs and 960 miRNAs that were differentially expressed after spinal cord injury. Of these, the expression levels of circPrkcsh were significantly different between injured and sham-treated mice. We then treated astrocytes with tumor necrosis factor-α in vitro to simulate the inflammatory response after spinal cord injury. Our results revealed an elevated expression of circPrkcsh with a concurrent decrease in miR-488 expression in injured cells. We also found that circPrkcsh regulated the expression of the inflammation-related gene Ccl2. Furthermore, in tumor necrosis factor-α-treated astrocytes, circPrkcsh knockdown decreased the expression of Ccl2 by upregulating miR-488 expression, and reduced the secretion of inflammatory cytokines in vitro. These findings suggest that differentially expressed circRNAs participate in the inflammatory response after spinal cord injury and act as the regulators of certain microRNAs. Furthermore, circPrkcsh may be used as an miR-488 sponge to regulate Ccl2 expression, which might provide a new potential therapy for SCI. The study was approved by the Animal Ethics Committee of Shandong University of China (approval No. KYLL-20170303) on March 3, 2017.

Key words: astrocyte, Ccl2, ceRNA, circRNA, inflammation, miR-488, ncRNA, Prkcsh, RNA sequencing, spinal cord injury