Genome-wide Analysis of Histone H3 Lysine 27 Trimethylation Profiles in Sciatic Nerve of Chronic Constriction Injury Rats

Chen, Shuhui; Gu, Xinpei; Li, Ruidi; An, Shuhong; Wang, Zhaojin

doi:10.1007/s11064-023-03879-y

Cited by 3 publications

(5 citation statements)

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“…In addition to forming myelin sheaths around axons and secreting neurotrophic factors, SCs can also regulate sensory perception and facilitate cell communications between synapses (Faroni et al, 2014). Moreover, it has been found that SCs also play a significant role in neuroinflammation and neuropathic pain (Wang et al, 2022;Adam et al, 2023;Chen et al, 2023).…”

Section: Schwann Cells and Peripheral Nerve Regeneration 21 Schwann C...mentioning

confidence: 99%

Progress in methods for evaluating Schwann cell myelination and axonal growth in peripheral nerve regeneration via scaffolds

Ling,

He,

Zhang

et al. 2023

Front. Bioeng. Biotechnol.

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Peripheral nerve injury (PNI) is a neurological disorder caused by trauma that is frequently induced by accidents, war, and surgical complications, which is of global significance. The severity of the injury determines the potential for lifelong disability in patients. Artificial nerve scaffolds have been investigated as a powerful tool for promoting optimal regeneration of nerve defects. Over the past few decades, bionic scaffolds have been successfully developed to provide guidance and biological cues to facilitate Schwann cell myelination and orientated axonal growth. Numerous assessment techniques have been employed to investigate the therapeutic efficacy of nerve scaffolds in promoting the growth of Schwann cells and axons upon the bioactivities of distinct scaffolds, which have encouraged a greater understanding of the biological mechanisms involved in peripheral nerve development and regeneration. However, it is still difficult to compare the results from different labs due to the diversity of protocols and the availability of innovative technologies when evaluating the effectiveness of novel artificial scaffolds. Meanwhile, due to the complicated process of peripheral nerve regeneration, several evaluation methods are usually combined in studies on peripheral nerve repair. Herein, we have provided an overview of the evaluation methods used to study the outcomes of scaffold-based therapies for PNI in experimental animal models and especially focus on Schwann cell functions and axonal growth within the regenerated nerve.

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Section: Schwann Cells and Peripheral Nerve Regeneration 21 Schwann C...mentioning

confidence: 99%

Progress in methods for evaluating Schwann cell myelination and axonal growth in peripheral nerve regeneration via scaffolds

Ling,

He,

Zhang

et al. 2023

Front. Bioeng. Biotechnol.

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“…The increased EZH2 protein expression in the anterior cingulate cortex was temporally accompanied by microglial activation and over-production of TNF-α, IL-1β, and IL-6 in the same area [ 11 ]. More recently, in rats with neuropathic pain induced by CCI, it was found that activation of Schwann cells (the peripheral subset of glial cells) in the damaged sciatic nerve resulted in increased expression of EZH2 and H3K27me3, which was associated with upregulation of IL-1α, MCP-1, BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) in the same nerve on postoperative days 1 to 14 [ 12 ]. The temporal correlation between the increased EZH2 protein expression and neuroinflammation along the pain signaling pathway (the peripheral nerve, spinal cord, and anterior cingulate cortex) in animals with neuropathic pain highly suggests that EZH2 may regulate neuropathic pain by regulating neuroinflammation.…”

Section: Regulation Of Neuroinflammation and Neuropathic Pain By Ezh2mentioning

confidence: 99%

“…In addition, activation of microglia and astrocytes and production of pro-inflammatory mediators (TNF-α, IL-1β, MCP-1) in the spinal cord induced by pSNL were all attenuated as well [ 9 ]. In rats with neuropathic pain induced by CCI, pre-emptive intrathecal [ 10 ] or intraperitoneal injection [ 12 ] of GSK126 prevented the development of mechanical and thermal hyperalgesia and reduced the enhanced protein expression of EZH2 and H3K27me3 in the spinal dorsal horn [ 10 ] and in the damaged sciatic nerve [ 12 ]. Intraperitoneal administration of GSK126 also reduced the levels of IL-1α, MCP-1, BDNF, and GDNF in the damaged sciatic nerve induced by CCI [ 12 ].…”

Section: Regulation Of Neuroinflammation and Neuropathic Pain By Ezh2mentioning

confidence: 99%

“…In rats with neuropathic pain induced by CCI, pre-emptive intrathecal [ 10 ] or intraperitoneal injection [ 12 ] of GSK126 prevented the development of mechanical and thermal hyperalgesia and reduced the enhanced protein expression of EZH2 and H3K27me3 in the spinal dorsal horn [ 10 ] and in the damaged sciatic nerve [ 12 ]. Intraperitoneal administration of GSK126 also reduced the levels of IL-1α, MCP-1, BDNF, and GDNF in the damaged sciatic nerve induced by CCI [ 12 ]. Furthermore, mechanical and cold allodynia induced by brachial plexus avulsion was attenuated when animals received systemic treatment with GSK-126 (7 mg/kg) (i.p.)…”

Section: Regulation Of Neuroinflammation and Neuropathic Pain By Ezh2mentioning

confidence: 99%

“…Recent studies by us [ 9 ] and others [ 10 , 11 , 12 , 13 , 14 , 15 ] have shown that enhancer of zeste homolog-2 (EZH2), a key subunit of polycomb complex 2 (PRC2), plays an important role in the genesis of neuropathic pain by regulating gene expression. Protein expression is regulated by transcriptional and post transcriptional processes.…”

Section: Introductionmentioning

confidence: 99%

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EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain

Weng

Taing

Chen

et al. 2023

Cells

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Recent studies by us and others have shown that enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, in glial cells regulates the genesis of neuropathic pain by modulating the production of proinflammatory cytokines and chemokines. In this review, we summarize recent advances in this research area. EZH2 is a subunit of polycomb repressive complex 2 (PRC2), which primarily serves as a histone methyltransferase to catalyze methylation of histone 3 on lysine 27 (H3K27), ultimately resulting in transcriptional repression. Animals with neuropathic pain exhibit increased EZH2 activity and neuroinflammation of the injured nerve, spinal cord, and anterior cingulate cortex. Inhibition of EZH2 with DZNep or GSK-126 ameliorates neuroinflammation and neuropathic pain. EZH2 protein expression increases upon activation of Toll-like receptor 4 and calcitonin gene-related peptide receptors, downregulation of miR-124-3p and miR-378 microRNAs, or upregulation of Lncenc1 and MALAT1 long noncoding RNAs. Genes suppressed by EZH2 include suppressor of cytokine signaling 3 (SOCS3), nuclear factor (erythroid-derived 2)-like-2 factor (NrF2), miR-29b-3p, miR-146a-5p, and brain-specific angiogenesis inhibitor 1 (BAI1). Pro-inflammatory mediators facilitate neuronal activation along pain-signaling pathways by sensitizing nociceptors in the periphery, as well as enhancing excitatory synaptic activities and suppressing inhibitory synaptic activities in the CNS. These studies collectively reveal that EZH2 is implicated in signaling pathways known to be key players in the process of neuroinflammation and genesis of neuropathic pain. Therefore, targeting the EZH2 signaling pathway may open a new avenue to mitigate neuroinflammation and neuropathic pain.

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Sirtuin 3 Mediated by Spinal cMyc–Enhancer of Zeste Homology 2 Pathway Plays an Important Role in Human Immunodeficiency Virus-Related Neuropathic Pain Model

Zhu,

Yi,

et al. 2024

Anesthesia &Amp; Analgesia

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BACKGROUND: Clinical data demonstrate that chronic use of opioid analgesics increases neuropathic pain in people living with human immunodeficiency virus (HIV). Therefore, it is important to elucidate the molecular mechanisms of HIV-related chronic pain. In this study, we investigated the role of the transcription factor cMyc, epigenetic writer enhancer of zeste homology 2 (EZH2), and sirtuin 3 (Sirt3) pathway in HIV glycoprotein gp120 with morphine (gp120M)-induced neuropathic pain in rats. METHODS: Neuropathic pain was induced by intrathecal administration of recombinant gp120 with morphine. Mechanical withdrawal threshold was measured using von Frey filaments, and thermal latency using the hotplate test. Spinal expression of cMyc, EZH2, and Sirt3 were measured using Western blots. Antinociceptive effects of intrathecal administration of antisense oligodeoxynucleotide against cMyc, a selective inhibitor of EZH2, or recombinant Sirt3 were tested. RESULTS: In the spinal dorsal horn, gp120M upregulated expression of cMyc (ratio of gp120M versus control, 1.68 ± 0.08 vs 1.00 ± 0.14, P = .0132) and EZH2 (ratio of gp120M versus control, 1.76 ± 0.05 vs 1.00 ± 0.16, P = .006), and downregulated Sirt3 (ratio of control versus gp120M, 1.00 ± 0.13 vs 0.43 ± 0.10, P = .0069) compared to control. Treatment with intrathecal antisense oligodeoxynucleotide against cMyc, GSK126 (EZH2 selective inhibitor), or recombinant Sirt3 reduced mechanical allodynia and thermal hyperalgesia in this gp120M pain model. Knockdown of cMyc reduced spinal EZH2 expression in gp120M treated rats. Chromatin immunoprecipitation (ChIP) assay showed that enrichment of cMyc binding to the ezh2 gene promoter region was increased in the gp120M-treated rat spinal dorsal horn, and that intrathecal administration of antisense ODN against cMyc (AS-cMyc) reversed the increased enrichment of cMyc. Enrichment of trimethylation of histone 3 on lysine residue 27 (H3K27me3; an epigenetic mark associated with the downregulation of gene expression) binding to the sirt3 gene promoter region was upregulated in the gp120M-treated rat spinal dorsal horn; that intrathecal GSK126 reversed the increased enrichment of H3K27me3 in the sirt3 gene promoter. Luciferase reporter assay demonstrated that cMyc mediated ezh2 gene transcription at the ezh2 gene promoter region, and that H3K27me3 silenced sirt3 gene transcription at the gene promoter region. CONCLUSION: These results demonstrated that spinal Sirt3 decrease in gp120M-induced neuropathic pain was mediated by cMyc–EZH2/H3K27me3 activity in an epigenetic manner. This study provided new insight into the mechanisms of neuropathic pain in HIV patients with chronic opioids.

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Genome-wide Analysis of Histone H3 Lysine 27 Trimethylation Profiles in Sciatic Nerve of Chronic Constriction Injury Rats

Cited by 3 publications

References 50 publications

Progress in methods for evaluating Schwann cell myelination and axonal growth in peripheral nerve regeneration via scaffolds

Progress in methods for evaluating Schwann cell myelination and axonal growth in peripheral nerve regeneration via scaffolds

EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain

Sirtuin 3 Mediated by Spinal cMyc–Enhancer of Zeste Homology 2 Pathway Plays an Important Role in Human Immunodeficiency Virus-Related Neuropathic Pain Model

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