MicroRNA-182 improves spinal cord injury in mice by modulating apoptosis and the inflammatory response via IKKβ/NF-κB

overexpression of the microRNA miR-182 promotes functional recovery and reduced histopathological changes in spinal cord injury mice. miR-182 overexpression reduces apoptosis and attenuates the inflammatory response in spinal cord tissues by blocking the IKK beta/NF-kappa B pathway. These findings suggest that upregulation of miR-182 may be a novel therapeutic target for SCI. Spinal cord injury (SCI) is one common neurological condition which involves primary injury and secondary injury. Neuron inflammation and apoptosis after SCI is the most important pathological process of this disease. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. First, by re-analysis of Gene Expression Omnibus dataset (accession GSE19890), miR-182 was selected for further study because of its suppressive effects on the inflammatory response in the various types of injuries. Functional experiments demonstrated that miR-182 overexpression promoted functional recovery, reduced histopathological changes, and alleviated spinal cord edema in mice. It was also observed that miR-182 overexpression reduced apoptosis and attenuated the inflammatory response in spinal cord tissue, as evidenced by the reduction of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1 beta, and the induction of IL-10. Using a lipopolysaccharide (LPS)-induced SCI model in BV-2 cells, we found that miR-182 was downregulated in the BV-2 cells following LPS stimulation, and upregulation of miR-182 improved LPS-induced cell damage, as reflected by the inhibition of apoptosis and the inflammatory response. I kappa B kinase beta (IKK beta), an upstream target of the NF-kappa B pathway, was directly targeted by miR-182 and miR-182 suppressed its translation. Further experiments revealed that overexpression of IKK beta reversed the anti-apoptosis and anti-inflammatory effects of miR-182 in LPS stimulated BV-2 cells. Finally, we found that miR-182 overexpression blocked the activation of the NF-kappa B signaling pathway in vitro and in vivo, as demonstrated by the downregulation of phosphorylated (p-) I kappa B-alpha and nuclear p-p65. Taken together, these data indicate that miR-182 improved SCI-induced secondary injury through inhibiting apoptosis and the inflammatory response by blocking the IKK beta/NF-kappa B pathway. Our findings suggest that upregulation of miR-182 may be a novel therapeutic target for SCI.