2. Academic Validation
  3. Regulating DNA methylation could reduce neuronal ischemia response and apoptosis after ischemia-reperfusion injury

Regulating DNA methylation could reduce neuronal ischemia response and apoptosis after ischemia-reperfusion injury

  • Gene. 2022 Aug 30;837:146689. doi: 10.1016/j.gene.2022.146689.
Yigang Lv 1,  Chi Zhang 2,  Huan Jian 1,  Yongfu Lou 1,  Yi Kang 1,  Weimin Deng 3,  Chaoyu Wang 1,  Wei Wang 1,  Shenghui Shang 1,  Mengfan Hou 1,  Wenyuan Shen 1,  Jing Xie 1,  Xueying Li 4,  Hengxing Zhou 5,  Shiqing Feng 6
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin 300052, PR China.
  • 2 Department of Orthopaedics, Shandong University Centre for Orthopaedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
  • 3 Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Department of Immunology, Tianjin Medical University, Tianjin 300070, PR China.
  • 4 Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Department of Immunology, Tianjin Medical University, Tianjin 300070, PR China; Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China. Electronic address: xueyingli@sdu.edu.cn.
  • 5 Department of Orthopaedics, Shandong University Centre for Orthopaedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China. Electronic address: zhouhengxing@sdu.edu.cn.
  • 6 Department of Orthopaedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin 300052, PR China; Department of Orthopaedics, Shandong University Centre for Orthopaedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China. Electronic address: sqfeng@tmu.edu.cn.
PMID: 35750086 DOI: 10.1016/j.gene.2022.146689
Abstract

Background: Ischemia-reperfusion injury (IRI) is an important pathophysiological condition that can cause cell injury and large-scale tissue injury in the nervous system. Previous studies have shown that epigenetic regulation may play a role in the pathogenesis of IRI.

Methods: In this study, we isolated mouse cortical neurons and constructed an oxygen-glucose deprivation/reoxygenation (OGD) model to explore the change in DNA methylation and its effect on the expression of corresponding genes.

Results: We found that DNA methylation in neurons increased with hypoxia duration and that hypermethylation of numerous promoters and 3'-untranslated regions increased. We performed Gene Ontology enrichment analysis to study gene function and Kyoto Encyclopedia of Genes and Genomes pathway analysis to identify the pathways associated with gene regulation. The results showed that hypermethylation-related genes expressed after OGD were related to physiological pathways such as neuronal projection, ion transport, growth and development, while hypomethylation-related genes were related to pathological pathways such as the external Apoptosis signaling pathway, neuronal death regulation, and regulation of oxidative stress. However, the changes in DNA methylation were specific for certain genes and may have been related to OGD-induced neuronal damage. Importantly, we integrated transcription and DNA methylation data to identify several candidate target genes, including hypomethylated Apoe, Pax6, Bmp4, and Ptch1 and hypermethylated Adora2a, Crhr1, Stxbp1, and Tac1. This study further indicated the effect of DNA methylation on gene function in brain IRI from the perspective of Epigenetics, and the identified genes may become new targets for achieving neuroprotection in the brain after IRI.

Keywords

Apoptosis; Bioinformatics; DNA methylation(5-mC); Epitranscriptome analysis; Ischaemia reperfusion injury(IRI); Oxidative stress; Oxygen glucose deprivation/reoxygenation(OGD/R).

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