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miR-21-5p inhibits neuropathic pain development via directly targeting C-C motif ligand 1 and tissue inhibitor of metalloproteinase-3 |
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| Authors: | Liang Zhong Weimin Xiao Fang Wang Juan Liu Li-Jun Zhi |
| Affiliation: | 1. Department of Anesthesiology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China Liang Zhong and Weimin Xiao contributed equally to this study.;2. The Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Liang Zhong and Weimin Xiao contributed equally to this study.;3. School of Medicine, Tongji University, Shanghai, China;4. Xuzhou Medical University, Huai'an, China;5. Department of Anesthesiology, Huai'an Second People', Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China |
| Abstract: | MicroRNAs (miRNA) play important roles in neuroinflammation and neuropathic pain development; however, the underlying mechanism requires further investigation. The expression of miR-21-5p was remarkably upregulated in chronic constrictive injury (CCI) rat model. A significant alleviated neuropathic pain development and reduced the expression of cytokines was observed in CCI rat after exogenous injection of miR-21-5p mimic. The dual-luciferase analysis revealed that tissue inhibitor of metalloproteinase-3 (TIMP3) and chemokines C-C motif ligand 1 (CCL1) was direct downstream target of miR-21-5p. Moreover, silencing of TIMP3 and CCL1 could rescue mechanical allodynia, thermal hyperalgesia and cytokine release in CCI rat, suggesting that TIMP3 and CCL1 exert their function by mediating neuroinflammation in neuropathic pain development. Therefore, we have identified a novel miR-21-5p–CCL1/TIMP3-cytokine axis in regulation of neuropathic pain development in CCI rat model, which is valuable for enhancing our understanding of neuropathic pain and developing miRNAs as potential therapeutic options in the future. |
| Keywords: | chemokines C-C motif ligand 1 (CCL1) inflammation miR-21-5p neuropathic pain tissue inhibitor of metalloproteinase-3 (TIMP3) |