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NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR
Nuclear factor of activated T cells (NFAT5) is a well-known transcription factor that regulates the expression of genes involved in osmotic stress. However, the role of NFAT5 in inflammatory pain remains unknown. Here, we studied the function of NFAT5 in inflammatory pain using NFAT5-heterozygous (H...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961436/ https://www.ncbi.nlm.nih.gov/pubmed/33806698 http://dx.doi.org/10.3390/ijms22052587 |
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author | Gwon, Do Hyeong Kim, Song I. Lee, Seoung Hun Noh, Chan Kim, Yeojung Yun, Sangwon Lee, Won Hyung Oh, Jun Young Kim, Dong Woon Hong, Jinpyo Lee, Sun Yeul |
author_facet | Gwon, Do Hyeong Kim, Song I. Lee, Seoung Hun Noh, Chan Kim, Yeojung Yun, Sangwon Lee, Won Hyung Oh, Jun Young Kim, Dong Woon Hong, Jinpyo Lee, Sun Yeul |
author_sort | Gwon, Do Hyeong |
collection | PubMed |
description | Nuclear factor of activated T cells (NFAT5) is a well-known transcription factor that regulates the expression of genes involved in osmotic stress. However, the role of NFAT5 in inflammatory pain remains unknown. Here, we studied the function of NFAT5 in inflammatory pain using NFAT5-heterozygous (Het) mice. To study inflammatory pain, we injected 10 µL of 2% formalin into the right hind paws of mice and monitored pain behaviors, such as licking, lifting, and flinching, for 60 min. After the first 15 min (phase I), there were no significant differences in pain behaviors between wild-type (WT) and NFAT5-Het mice. However, from 15–60 min (phase II), NFAT5-Het mice displayed significantly fewer pain behaviors compared to WT mice. Further, the expression levels of inflammatory-pain-related factors, including c-Fos, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated n-methyl-D-aspartate receptor subunit 2B (p-NR2B), were significantly elevated in the spinal dorsal neurons of formalin-treated WT mice but was not elevated in NFAT5-Het mice. Similarly, c-Fos, p-ERK, and p-NR2B levels were significantly higher in glutamate-treated PC12 neuronal cells but were not affected by Nfat5 silencing in glutamate-treated PC12 cells. Altogether, our findings suggest that NFAT5 deficiency may mitigate formalin-induced inflammatory pain by upregulating mammalian target of rapamycin (mTOR) expression and downregulating its downstream factors in spinal dorsal neurons. Therefore, NFAT5 is a potential therapeutic target for the treatment of inflammatory pain. |
format | Online Article Text |
id | pubmed-7961436 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79614362021-03-17 NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR Gwon, Do Hyeong Kim, Song I. Lee, Seoung Hun Noh, Chan Kim, Yeojung Yun, Sangwon Lee, Won Hyung Oh, Jun Young Kim, Dong Woon Hong, Jinpyo Lee, Sun Yeul Int J Mol Sci Article Nuclear factor of activated T cells (NFAT5) is a well-known transcription factor that regulates the expression of genes involved in osmotic stress. However, the role of NFAT5 in inflammatory pain remains unknown. Here, we studied the function of NFAT5 in inflammatory pain using NFAT5-heterozygous (Het) mice. To study inflammatory pain, we injected 10 µL of 2% formalin into the right hind paws of mice and monitored pain behaviors, such as licking, lifting, and flinching, for 60 min. After the first 15 min (phase I), there were no significant differences in pain behaviors between wild-type (WT) and NFAT5-Het mice. However, from 15–60 min (phase II), NFAT5-Het mice displayed significantly fewer pain behaviors compared to WT mice. Further, the expression levels of inflammatory-pain-related factors, including c-Fos, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated n-methyl-D-aspartate receptor subunit 2B (p-NR2B), were significantly elevated in the spinal dorsal neurons of formalin-treated WT mice but was not elevated in NFAT5-Het mice. Similarly, c-Fos, p-ERK, and p-NR2B levels were significantly higher in glutamate-treated PC12 neuronal cells but were not affected by Nfat5 silencing in glutamate-treated PC12 cells. Altogether, our findings suggest that NFAT5 deficiency may mitigate formalin-induced inflammatory pain by upregulating mammalian target of rapamycin (mTOR) expression and downregulating its downstream factors in spinal dorsal neurons. Therefore, NFAT5 is a potential therapeutic target for the treatment of inflammatory pain. MDPI 2021-03-04 /pmc/articles/PMC7961436/ /pubmed/33806698 http://dx.doi.org/10.3390/ijms22052587 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gwon, Do Hyeong Kim, Song I. Lee, Seoung Hun Noh, Chan Kim, Yeojung Yun, Sangwon Lee, Won Hyung Oh, Jun Young Kim, Dong Woon Hong, Jinpyo Lee, Sun Yeul NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR |
title | NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR |
title_full | NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR |
title_fullStr | NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR |
title_full_unstemmed | NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR |
title_short | NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR |
title_sort | nfat5 deficiency alleviates formalin-induced inflammatory pain through mtor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961436/ https://www.ncbi.nlm.nih.gov/pubmed/33806698 http://dx.doi.org/10.3390/ijms22052587 |
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