MiR-223 Inhibits the Polarization and Recruitment of Macrophages via NLRP3/IL-1β Pathway to Meliorate Neuropathic Pain.

Junsong Zhu,Jianguo Xu,Jinmei Yang,Massimiliano Valeriani

doi:10.1155/2021/6674028

Abstract

Background miRNA is an essential factor in neuropathic pain. However, the underlying mechanism of miRNA in neuropathic pain remains unclear. Objective To explore the potential role of miR-223 in neuropathic pain in a mice model of chronic sciatic nerve injury. Methods Mice were divided into the sham group, CCI group, CCI + Lenti-vector group, and CCI + Lenti-miR-223 group. Flow cytometry was used to detect the neuronal apoptosis and the proportion of M1/M2 macrophages in each group. Western blot was used to detect the protein expression levels of ASC, caspase-1, IL-1β, and IL-18 in each group. Luciferase activity assay detects the binding of miR-223 and NLRP3. Macrophage chemotaxis experiments verified the anti-inflammatory effect of miR-223 in vitro. Results The overexpression of miR-233 significantly reduced the neuropathic pain caused by CCI and reduced the apoptosis and inflammatory factor expression. miR-223 inhibits the expression of NLRP3 by directly binding to the 3′-untranslated region. Overexpression of miR-223 reduces the protein levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in the spinal cord of CCI mice, increases the proportion of M2-type macrophages, and reduces the proportion of M1-type macrophages. Conclusion miR-223 may facilitate the development of neuropathic pain in CCI mice by inhibiting NLRP3-mediated neuroinflammation.

Highlights

Neuropathic pain refers to pain caused by the damage to the somatosensory system or disease
In order to study the relationship between miR-223 and neuropathic pain, mice with chronic sciatic nerve contraction were produced by surgical ligation, and the expression of miR-223 in the spinal cord was measured at 0, 3, 7, 14, and 0, respectively, 21 days after CCI. e spinal cord of the mice was collected and analyzed for miR-223 levels in the spinal cord by qRT-PCR analysis. e data showed that in CCI mice, miR-223 was significantly downregulated compared to mice undergoing sham surgery (Figure 1(a))
To further study the biological role of miR-223 in neuropathic pain, miR-223 was overexpressed in mice by intrathecal injection of lentivirus to express miR-223

Summary

Introduction

Neuropathic pain refers to pain caused by the damage to the somatosensory system or disease. MiR-223 plays a crucial role in inflammatory diseases by regulating different gene transcription factors (including C/EBPa, E2F1, and NF-κB pathway) [8]. The underlying mechanism of miRNA in neuropathic pain remains unclear. To explore the potential role of miR-223 in neuropathic pain in a mice model of chronic sciatic nerve injury. E overexpression of miR-233 significantly reduced the neuropathic pain caused by CCI and reduced the apoptosis and inflammatory factor expression. Overexpression of miR-223 reduces the protein levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in the spinal cord of CCI mice, increases the proportion of M2-type macrophages, and reduces the proportion of M1-type macrophages. MiR-223 may facilitate the development of neuropathic pain in CCI mice by inhibiting NLRP3mediated neuroinflammation Conclusion. miR-223 may facilitate the development of neuropathic pain in CCI mice by inhibiting NLRP3mediated neuroinflammation

Methods

Results

Conclusion