中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (11): 2123-2130.doi: 10.4103/1673-5374.280323

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

脊髓缺血再灌注损伤中的miRNAs调控模式

  

  • 出版日期:2020-11-15 发布日期:2020-08-23
  • 基金资助:

    国家自然科学基金(81350013)

MicroRNA regulatory pattern in spinal cord ischemia- reperfusion injury

Zhi-Gang Liu1 , Yin Li2 , Jian-Hang Jiao1 , Hao Long3 , Zhuo-Yuan Xin4 , Xiao-Yu Yang1   

  1. 1 Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin Province, China
    2 School of Public Health, Jilin University, Changchun, Jilin Province, China
    3 Pain Clinic, The Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
    4 The Key Laboratory of Zoonosis Search, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin Province, China
  • Online:2020-11-15 Published:2020-08-23
  • Contact: Xiao-Yu Yang, PhD,yangxiaoyu88@sina.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81350013 (to XYY).

摘要:

脊髓损伤后会出现miRNA失调,而失调miRNA可通过多种途径参与SCI后的炎性反应,细胞凋亡、轴突再生的抑制过程,但其在脊髓缺血再灌注损伤中的作用尚不明确。为此,实验采用了miRNA芯片技术,检测了包括大鼠脊髓缺血90 min后充血再灌注24 h以及48 h组脊髓组织样本的miRNA表达谱数据,希望通过生物信息学分析方法,分别建立此2组中发生异常表达的miRNA分子调控网络,发现该网络要参与了细胞生存、细胞增殖以及细胞凋亡等生物过程,实验结果可见:(1)MAPK信号转导通路在两组中同时被显著富集;(2)生物信息学分析及qRT-PCR检测均验证了miR-22-3p在两组病变脊髓组织中持续高表达这一结果;(3)上述数据证实,脊髓缺血再灌注损伤后异常表达miRNAs分子调控网络可能受MAPK信号通路调节,持续性地影响细胞生理生化状态从而参与脊髓缺血再灌注损伤调控,miR-22-3p在脊髓缺血再灌注损伤过程中发挥持续性损伤调控作用。

orcid: 0000-0003-2516-440X (Xiao-Yu Yang)

关键词: 基因调控网络, miRNA, 微阵列, miR-22-3p, MAPK信号通路, 神经再生, 脊髓缺血再灌注损伤, 转录组

Abstract: After spinal cord injury, dysregulated miRNAs appear and can participate in inflammatory responses, as well as the inhibition of apoptosis and axon regeneration through multiple pathways. However, the functions of miRNAs in spinal cord ischemia-reperfusion injury pro- gression remain unclear. miRCURY LNATM Arrays were used to analyze miRNA expression profiles of rats after 90 minutes of ischemia followed by reperfusion for 24 and 48 hours. Furthermore, subsequent construction of aberrantly expressed miRNA regulatory patterns involved cell survival, proliferation, and apoptosis. Remarkably, the mitogen-activated protein kinase (MAPK) signaling pathway was the most significantly enriched pathway among 24- and 48-hour groups. Bioinformatics analysis and quantitative reverse transcription poly- merase chain reaction confirmed the persistent overexpression of miR-22-3p in both groups. These results suggest that the aberrant miRNA regulatory network is possibly regulated MAPK signaling and continuously affects the physiological and biochemical status of cells, thus participating in the regulation of spinal cord ischemia-reperfusion injury. As such, miR-22-3p may play sustained regulatory roles in spinal cord ischemia-reperfusion injury. All experimental procedures were approved by the Animal Ethics Committee of Jilin University, China [approval No. 2020 (Research) 01].

Key words: gene regulatory networks, microarray analysis, microRNA, miR-22-3p, mitogen-activated protein kinase signaling pathway, nerve
regeneration,
neural regeneration, spinal cord ischemia-reperfusion injury, transcriptome