YY1 promotes SOCS3 expression to inhibit STAT3mediated neuroinflammation and neuropathic pain.
Mol Med Rep
; 23(2)2021 02.
Article
em En
| MEDLINE
| ID: mdl-33300076
ABSTRACT
Neuropathic pain is induced by primary injury and dysfunction of the nervous system, and is accompanied by the activation of inflammation signaling pathways. Yin Yang 1 (YY1) is reported to be involved in inflammation; however, its role in the development of neuropathic pain is still unclear. In the present study, a neuropathic pain model was established using the bilateral chronic constriction injury (bCCI) method in rats. The indexes of neuropathic pain were detected, including paw mechanical withdrawal threshold (MWT), paw thermal withdrawal latency (PTWL) and paw frequency in response to cold stimulus, characterizing the symptoms of mechanical allodynia, thermal hyperalgesia and cold hyperalgesia, respectively. YY1 mRNA expression was significantly decreased in the spinal cord cells of bCCI rats. In addition, YY1 was overexpressed in the bCCI rats by intrathecally injecting different doses of the pcDNAYY1. YY1 reduced rat mechanical allodynia, thermal hyperalgesia and cold hyperalgesia in a dosedependent manner. Furthermore, YY1 increased the expression of suppressor of cytokine signaling 3 (SOCS3) and suppressed signal transducer and activator of transcription 3 (STAT3)mediated production of inflammatory factors in a dosedependent manner. Finally, YY1 were respectively overexpressed and knocked down in primary spinal cord cells. The results revealed that YY1 overexpression promoted SOCS3 expression, increased cell proliferation and suppressed cell apoptosis, and reduced the activation of STAT3 and STAT3mediated production of inflammatory factors. YY1 knockdown induced the opposite effect to that observed following YY1 overexpression. Furthermore, blockade of SOCS3 by SOCS3antibody abrogated the effect of YY1 overexpression on the suppression of SOCS3mediated STAT3 activation and inflammation. In conclusion, YY1 alleviated neuropathic pain by inhibiting the STAT3 signaling pathway, which may be due to the upregulation of SOCS3 expression.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Regulação da Expressão Gênica
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Fator de Transcrição STAT3
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Fator de Transcrição YY1
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Proteína 3 Supressora da Sinalização de Citocinas
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Neuralgia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article