miR-506-3p Relieves Neuropathic Pain following Brachial Plexus Avulsion via Mitigating Microglial Activation through Targeting the CCL2-CCR2 Axis

Abstract

Neuroinflammation results in neuropathic pain following brachial plexus avulsion (BPA). This research was designed for investigating the function of miR-506-3p in BPA-induced neuropathic pain (NP). A total brachial plexus root avulsion (tBPRA) model was produced in adult rats as well as IL-1β-treated motoneuron-like NSC-34 cells and the LPS-treated microglia cell line BV2 for in vivo and in vitro experiments, respectively. RT-PCR and western blot were performed to detect the profiles of miR-506-3p, CCL2 and CCR2, NF-κB, FOXO3a, TNF-α, IL-1β, and IL-6 in cells or the spinal cord close to the tBPI lesion. Neuronal apoptosis was evaluated by immunohistochemistry (IHC) in vivo. CCK8, TUNEL staining, and the LDH kit were adopted for the evaluation of neuronal viability or damage in vitro. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assays analyzed the targeted association between miR-506-3p and CCL2. As shown by the data, miR-506-3p was vigorously less expressed, while CCL2-CCR2, NF-κB TNF-α, IL-1β, and IL-6 were up-regulated in the spinal cord with tBPI. Overexpression of miR-506-3p attenuated neuronal apoptosis and microglial inflammation. Mechanistically, CCL2 was a downstream target of miR-506-3p. Up-regulating miR-506-3p dampened CCL2-CCR2 and NF-κB activation in the spinal cord and microglia. miR-506-3p had neuroprotective and inflammation-fighting functions in the tBPI rat model via CCL2/CCR2/NF-κB axis.

Sepsis‐associated encephalopathy: Autophagy and miRNAs regulate microglial activation

“…It was reported that in a neonatal rat model of cerebral ischemia and hypoxia, miR‐210 induces the polarization of microglia toward the M1 phenotype partly by targeting SIRT1, which reduces the deacetylation of the NF‐κB subunit p65 and increases NF‐κB signaling (Li et al., 2020 ). Finally, upregulation of microRNA‐506‐3p was shown to exert neuroprotective and anti‐inflammatory effects, and microRNA‐506‐3p inhibited microglial activation by targeting the CCL2‐CCR2 axis (Jin et al., 2023 ). In summary, microRNAs can directly or indirectly regulate the polarization of microglia (e.g., microRNAs can regulate microglial activation by regulating autophagy).…”

Engineered Macrophage Membrane‐Coated Nanoparticles with Enhanced CCR2 Expression Promote Spinal Cord Injury Repair by Suppressing Neuroinflammation and Neuronal death

“…[9,10] The multiple roles of CCL2 in SCI pathology make the CCL2-CCR2 axis an attractive therapeutic target for SCI treatment. [11][12][13] However, to the best of our knowledge, there are currently limited effective drugs that target the CCL2-CCR2 axis for the treatment of SCI.…”