中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (3): 596-600.doi: 10.4103/1673-5374.290914

• 原著:脑损伤修复保护与再生 • 上一篇    

GCH1调控的链非编码RNA 可作为神经性疼痛中小胶质细胞活化的靶标

  

  • 出版日期:2021-03-15 发布日期:2020-12-17
  • 基金资助:

    中国国际自然科学基金项目(8157220581974345

Guanosine-5′-triphosphate cyclohydrolase 1 regulated long noncoding RNAs are potential targets for microglial activation in neuropathic pain 

Yan-Hu Liang1, 2, Guo-Wu Chen2, 3, Xue-Song Li4, Shu Jia2, Chun-Yang Meng2, 3, *   

  1. 1 Department of Clinical Medical College, Jining Medical University, Jining, Shandong Province, China;  2 Neuropathic Pain Institute for Spinal Nerve of Jining Medical University, Jining, Shandong Province, China;  3 Department of Spine Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China;  4 Department of Joint Surgery, Yanzhou Campus, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China 
  • Online:2021-03-15 Published:2020-12-17
  • Contact: Chun-Yang Meng, MD, PhD, mengchunyang1600@mail.jnmc.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81572205 and 81974345 (both to CYM).

摘要:

多项研究已证实小胶质细胞参与神经性疼痛,而抑制GTP环水解酶1可减少小胶质细胞的炎症反应,但其调节神经性疼痛的具体作用机制尚不明确。为此,实验设计以腺病毒转染小胶质细胞从而敲低GTP环水解酶1表达,经高通量测序发现在GO分析的分子功能中最下调的是丝裂原活化蛋白激酶相关通路和蛋白。同时在GO分析中选择丝裂原活化蛋白激酶与相关的5个长链非编码RNA进行共表达网络分析,发现与丝裂原活化蛋白激酶14 具有密切相关性。通过实时荧光定量PCR验证发现,长链非编码RNA中的ENSMUST00000205634,ENSMUST00000218450,ENSMUST00000156079与丝裂原活化蛋白激酶14 mRNA表达下调有关。这为GTP环水解酶1参与神经性疼痛提供了一些新的潜在靶点。研究首次概述GTP环水解酶1基因敲除的BV2小胶质细胞中差异表达的长链非编码RNA和mRNA,揭示了GTP环水解酶1在小胶质细胞激活中的机制,这可能为神经性疼痛中的小胶质细胞活化提供新的靶标。

https://orcid.org/0000-0002-3334-9503 (Chun-Yang Meng)

关键词: 疼痛, RNA, 细胞, 小胶质细胞, 蛋白, 因子, 通路, 炎症

Abstract: Several studies have confirmed that microglia are involved in neuropathic pain. Inhibition of guanosine-5′-triphosphate cyclohydrolase 1 (GTPCH1) can reduce the inflammation of microglia. However, the precise mechanism by which GTPCH1 regulates neuropathic pain remains unclear. In this study, BV2 microglia were transfected with adenovirus to knockdown GTPCH1 expression. High throughput sequencing analysis revealed that the mitogen-activated protein kinase (MAPK) related pathways and proteins were the most significantly down-regulated molecular function. Co-expression network analysis of Mapk14 mRNA and five long noncoding RNAs (lncRNAs) revealed their correlation. Quantitative reverse transcription-polymerase chain reaction revealed that among five lncRNAs, ENSMUST00000205634, ENSMUST00000218450 and ENSMUST00000156079 were related to the downregulation of Mapk14 mRNA expression. These provide some new potential targets for the involvement of GTPCH1 in neuropathic pain. This study is the first to note the differential expression of lncRNAs and mRNA in GTPCH1 knockdown BV2 microglia. Findings from this study reveal the mechanism by which GTPCH1 activates microglia and provide new potential targets for microglial activation in neuropathic pain. 

Key words: cells, factors, inflammation, microglia, pain, pathway, protein, RNA