YY1 promotes SOCS3 expression to inhibit STAT3‑mediated neuroinflammation and neuropathic pain

Sun,Manyi; Sun,Yue; Ma,Jinfeng; Li,Kezhong

doi:10.3892/mmr.2020.11742

YY1 promotes SOCS3 expression to inhibit STAT3‑mediated neuroinflammation and neuropathic pain

Authors:
- Manyi Sun
- Yue Sun
- Jinfeng Ma
- Kezhong Li
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Affiliations: Department of Anesthesiology, The Second Affiliated Hospital, College of Medicine, Shandong University, Jinan, Shandong 250033, P.R. China, Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China, Department of Anesthesiology, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China
Published online on: December 1, 2020 https://doi.org/10.3892/mmr.2020.11742
Article Number: 103

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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 pcDNA‑YY1. YY1 reduced rat mechanical allodynia, thermal hyperalgesia and cold hyperalgesia in a dose‑dependent 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 dose‑dependent 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 STAT3‑mediated production of inflammatory factors. YY1 knockdown induced the opposite effect to that observed following YY1 overexpression. Furthermore, blockade of SOCS3 by SOCS3‑antibody abrogated the effect of YY1 overexpression on the suppression of SOCS3‑mediated 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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