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Down-regulation of MAPK pathway alleviates TRPV4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation
Our objective of this study is to determine the molecular mechanism of MAPKs (mitogen activated protein kinase systems) on TRPV4 (transient receptor potential vanilloid 4)-mediated trigeminal neuralgia (TN). Partial chronic constriction injury of the infraorbital nerve (CCI-ION) ligation model was u...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541954/ https://www.ncbi.nlm.nih.gov/pubmed/34499186 http://dx.doi.org/10.1007/s00221-021-06194-6 |
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author | Liu, Weidong Pu, Benfang Liu, Mindi Zhang, Xuejun Zeng, Ran |
author_facet | Liu, Weidong Pu, Benfang Liu, Mindi Zhang, Xuejun Zeng, Ran |
author_sort | Liu, Weidong |
collection | PubMed |
description | Our objective of this study is to determine the molecular mechanism of MAPKs (mitogen activated protein kinase systems) on TRPV4 (transient receptor potential vanilloid 4)-mediated trigeminal neuralgia (TN). Partial chronic constriction injury of the infraorbital nerve (CCI-ION) ligation model was used in this research. When treated with antagonists of p38, JNK or ERK, the mechanical hyperalgesia threshold, nerve fiber disorder, myelinoclasis, and Schwann cells proliferation could be reversed. RT-PCR (real-time quantitative polymerase chain reaction), Western blot and IHC (immunohistochemistry) showed that TRPV4 mRNA and protein levels, TRPV4-positive cells and small positive neurons decreased remarkably in TN group treated with antagonists of p38, JNK or ERK. ELISA (enzyme-linked immunosorbent assay) was performed to discover inhibition of MAPK pathway can down-regulate the expression of HATs (histone acetyltransferases), and up-regulate the expression of HDACs (histone deacetylases) in TN, thus inhibiting histone acetylation. Finally, Western blot was performed to identify the phosphorylation status of p38, JNK and ERK, finding decreased phosphorylation forms in antagonists treated TN groups compared with TN groups. Based on the above investigation method, on a whole, our study showed that down-regulation of MAPK pathway could alleviate TRPV4-mediated trigeminal neuralgia, via inhibiting the activation of histone acetylation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00221-021-06194-6. |
format | Online Article Text |
id | pubmed-8541954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-85419542021-10-27 Down-regulation of MAPK pathway alleviates TRPV4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation Liu, Weidong Pu, Benfang Liu, Mindi Zhang, Xuejun Zeng, Ran Exp Brain Res Research Article Our objective of this study is to determine the molecular mechanism of MAPKs (mitogen activated protein kinase systems) on TRPV4 (transient receptor potential vanilloid 4)-mediated trigeminal neuralgia (TN). Partial chronic constriction injury of the infraorbital nerve (CCI-ION) ligation model was used in this research. When treated with antagonists of p38, JNK or ERK, the mechanical hyperalgesia threshold, nerve fiber disorder, myelinoclasis, and Schwann cells proliferation could be reversed. RT-PCR (real-time quantitative polymerase chain reaction), Western blot and IHC (immunohistochemistry) showed that TRPV4 mRNA and protein levels, TRPV4-positive cells and small positive neurons decreased remarkably in TN group treated with antagonists of p38, JNK or ERK. ELISA (enzyme-linked immunosorbent assay) was performed to discover inhibition of MAPK pathway can down-regulate the expression of HATs (histone acetyltransferases), and up-regulate the expression of HDACs (histone deacetylases) in TN, thus inhibiting histone acetylation. Finally, Western blot was performed to identify the phosphorylation status of p38, JNK and ERK, finding decreased phosphorylation forms in antagonists treated TN groups compared with TN groups. Based on the above investigation method, on a whole, our study showed that down-regulation of MAPK pathway could alleviate TRPV4-mediated trigeminal neuralgia, via inhibiting the activation of histone acetylation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00221-021-06194-6. Springer Berlin Heidelberg 2021-09-09 2021 /pmc/articles/PMC8541954/ /pubmed/34499186 http://dx.doi.org/10.1007/s00221-021-06194-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Liu, Weidong Pu, Benfang Liu, Mindi Zhang, Xuejun Zeng, Ran Down-regulation of MAPK pathway alleviates TRPV4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation |
title | Down-regulation of MAPK pathway alleviates TRPV4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation |
title_full | Down-regulation of MAPK pathway alleviates TRPV4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation |
title_fullStr | Down-regulation of MAPK pathway alleviates TRPV4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation |
title_full_unstemmed | Down-regulation of MAPK pathway alleviates TRPV4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation |
title_short | Down-regulation of MAPK pathway alleviates TRPV4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation |
title_sort | down-regulation of mapk pathway alleviates trpv4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541954/ https://www.ncbi.nlm.nih.gov/pubmed/34499186 http://dx.doi.org/10.1007/s00221-021-06194-6 |
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