title: Down-Regulation of miRNA-128 Contributes to Neuropathic Pain Following Spinal Cord Injury via Activation of P38.
abstract: BACKGROUND Neuropathic pain (NPP) arises from a lesion or dysfunction of the somatosensory nervous system. Recent studies have demonstrated multiple microRNAs (miRNAs) play key roles in NPP development. This study aimed to investigate the effects of miR-128 on microglial cells. MATERIAL AND METHODS We established a compressive spinal cord injury (SCI) model and collected the spinal cord segment-derived conditioned medium (CM). We then measured the expression of miR-128 in the murine microglial cell line BV2 treated with CM-SCI or CM obtained from control (CM-NC). Furthermore, lentivirus production of miR-128 and scrambled control were transfected into BV2 cells, which were first treated with CM-SCI or CM-NC. Moreover, the effects of miR-128 on cell viability, M1/M2 microglial gene expression, inflammatory cytokines concentration, and the protein expression of P38 and phosphorylated P38 (P-P38) were investigated. RESULTS The expression of miR-128 was downregulated in murine microglial BV2 cells treated with CM-SCI. Overexpression of miR-128 markedly promoted the viability of murine microglial cells. In addition, miR-128 overexpression significantly decreased the expression levels of microglial M1 phenotypic markers CD86 and CD32, and increased the expression levels of M2 phenotypic markers Arg1 and CD206. Furthermore, miR-128 overexpression obviously decreased the concentration of TNF-α, IL-1β, and IL-6. We found that miR-128 overexpression significantly downregulated the expression levels of P38 andP-P38. CONCLUSIONS Our findings indicate that down-regulation of miR-128 in murine microglial cells may contribute to the development of NPP following SCI via activation of P38. MiR-128 may be a potential intervention target for NPP.
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China (mainland).
authors.forename: Zhaoyun
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China (mainland).
authors.forename: Junmei
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China (mainland).
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China (mainland).
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009437:Neuralgia / Q000201:enzymology* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; C557010:MIRN128 microRNA, rat; D035683:MicroRNAs; D048051:p38 Mitogen-Activated Protein Kinases