• Neuroscience · Apr 2020

    Upregulation of Myeloid Zinc Finger 1 in DRG via Regulating MMP-2/9 and Kv 1.2 Expression Contributes to CFA-induced Inflammatory Pain.

    • Qin Niu, Fei Xing, Han-Wen Gu, Liying Bai, Jian Zhang, Jing-Jing Yuan, Yuan-Yuan Mao, Zhi-Song Li, Wei Zhang, and Ji-Tian Xu.
    • Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, P.R. China; Department of Anaesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital, Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450052, P.R. China.
    • Neuroscience. 2020 Apr 15; 432: 174-187.

    AbstractMyeloid zinc finger 1 (MZF1) belongs to the Kruppel family of zinc-finger transcription factors. Recent studies have demonstrated that in dorsal root ganglion (DRG) neurons, MZF1 is involved in the development and maintenance of neuropathic pain. However, the role of MZF1 in inflammatory pain still remains unknown. In the present study, the mechanism of MZF1 in chronic inflammatory pain was investigated in rats received an intraplantar injection of complete Freund's adjuvant (CFA). Subsequently, a series of assays including Western blotting, qRT-PCR, immunohistochemistry, and chromatin immunoprecipitation (ChIP) were performed. We found that CFA led to MZF1 upregulation in ipsilateral L4/5 DRGs. Pre- and post-microinjection of MZF1 siRNA into the ipsi-L5 DRG blocked the development of CFA-induced chronic inflammatory pain and alleviated the mechanical allodynia and thermal hyperalgesia in the maintenance phase. CFA also increased MMP-2/9 and Nav1.8 expression but reduced voltage-gated potassium 1.2 (Kv1.2) and Cav1.2 expression in L4/L5 DRGs. Microinjection of MZF1 siRNA into DRG diminished the CFA-induced changes in MMP-2/9 and Kv1.2 expression. However, the expressions of Nav1.8 and Cav1.2 were not changed by the treatment. Double immunofluorescence staining showed that MMP-2/9 and Kv1.2 were co-localized with MZF1 in DRGs. The ChIP-PCR results revealed that MZF1 binds directly to the promoter region of MMP-2/9 gene. Together, the above results imply that upregulation of MZF1 in DRGs might contribute to the development and maintenance of CFA-induced chronic inflammatory pain by regulating MMP-2/9 and Kv1.2 expression. Targeting DRG-localized MZF1 might be a promising therapeutic strategy for the treatment of chronic inflammatory pain in the clinic.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

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