EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain
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 res...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/7/1058 |
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| author | Han-Rong Weng Kyle Taing Lawrence Chen Angela Penney |
| author_facet | Han-Rong Weng Kyle Taing Lawrence Chen Angela Penney |
| author_sort | Han-Rong Weng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T05:41:23Z |
| format | Article |
| id | doaj.art-e537250281a44525aff16f220a18f006 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T05:41:23Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e537250281a44525aff16f220a18f0062023-11-17T16:28:42ZengMDPI AGCells2073-44092023-03-01127105810.3390/cells12071058EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic PainHan-Rong Weng0Kyle Taing1Lawrence Chen2Angela Penney3Department of Basic Sciences, California Northstate University College of Medicine, Elk Grove, CA 95757, USADepartment of Basic Sciences, California Northstate University College of Medicine, Elk Grove, CA 95757, USADepartment of Basic Sciences, California Northstate University College of Medicine, Elk Grove, CA 95757, USADepartment of Basic Sciences, California Northstate University College of Medicine, Elk Grove, CA 95757, USARecent 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.https://www.mdpi.com/2073-4409/12/7/1058epigeneticnociceptionSchwann cellsanalgesicsncRNA |
| spellingShingle | Han-Rong Weng Kyle Taing Lawrence Chen Angela Penney EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain Cells epigenetic nociception Schwann cells analgesics ncRNA |
| title | EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain |
| title_full | EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain |
| title_fullStr | EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain |
| title_full_unstemmed | EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain |
| title_short | EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain |
| title_sort | ezh2 methyltransferase regulates neuroinflammation and neuropathic pain |
| topic | epigenetic nociception Schwann cells analgesics ncRNA |
| url | https://www.mdpi.com/2073-4409/12/7/1058 |
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