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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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Autores principales: Weng, Han-Rong, Taing, Kyle, Chen, Lawrence, Penney, Angela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093242/
https://www.ncbi.nlm.nih.gov/pubmed/37048131
http://dx.doi.org/10.3390/cells12071058
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author Weng, Han-Rong
Taing, Kyle
Chen, Lawrence
Penney, Angela
author_facet Weng, Han-Rong
Taing, Kyle
Chen, Lawrence
Penney, Angela
author_sort Weng, Han-Rong
collection PubMed
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.
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spelling pubmed-100932422023-04-13 EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain Weng, Han-Rong Taing, Kyle Chen, Lawrence Penney, Angela Cells Review 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. MDPI 2023-03-31 /pmc/articles/PMC10093242/ /pubmed/37048131 http://dx.doi.org/10.3390/cells12071058 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Weng, Han-Rong
Taing, Kyle
Chen, Lawrence
Penney, Angela
EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain
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 Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093242/
https://www.ncbi.nlm.nih.gov/pubmed/37048131
http://dx.doi.org/10.3390/cells12071058
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