Abstract
Secondary injury after spinal cord injury (SCI) is one reversible pathological change mainly involving excessive inflammatory response and neuro-apoptosis. Since in recent years, microRNAs (miRNAs) have been proposed as novel regulators of inflammation in different disease conditions. However, the role of miRNAs in the inflammatory response and apoptosis of secondary injury after SCI remains to be fully elucidated. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. The expression profiles of miRNA were examined using miRNA microarray, and among the candidate miRNAs, miR-129-5p was found to be the most down-regulated miRNA in spinal tissues. Overexpression of miR-129-5p using agomir-miR-129-5p promoted injury mice functional recovery, suppressed the apoptosis and alleviated inflammatory response in spinal tissues. Using LPS-induced BV-2 cell model, we found miR-129-5p was also proved in protecting inflammatory response and cell apoptosis in vitro. High-mobility group protein B1 (HMGB1), a well-known inflammatory mediator, was found to be directly targeted by miR-129-5p and it was associated with the inhibitory effect of miR-129-5p on the activation of toll-like receptor (TLR)-4 (TLR4)/ nuclear factor-κB (NF-κB) pathway in vitro and in vivo. Further experiments revealed that the anti-apoptosis and anti-inflammatory effects of miR-129-5p were reversed by HMGB1 overexpression in BV-2 cells. Collectively, these data revealed that miR-129-5p alleviated SCI in mice via suppressing the apoptosis and inflammatory response through HMGB1//TLR4/NF-κB pathway. Our data suggest that up-regulation of miR-129-5p may be a novel therapeutic target for SCI.
Highlights
Spinal cord injury (SCI) is a traumatic injury that results in permanent impairment of the strength in the parts of the body served by the spinal cord below the levels of the injury
A number of studies demonstrated that miRNAs are aberrantly expressed in SCI, and may influence secondary SCI pathophysiology, such as inflammation and apoptosis [24,42,43]
Xu et al found that miR-124 improved functional recovery and suppressed neuronal cell apoptosis by blocking the mitochondrial apoptotic pathway in SCI rats [44]
Summary
Spinal cord injury (SCI) is a traumatic injury that results in permanent impairment of the strength in the parts of the body served by the spinal cord below the levels of the injury. The annual incidence rate of SCI are still ∼23 cases per million every year [1]. Many therapies have been explored for the improvement of patients with SCI, all demonstrated limited efficacy far. SCI is characterized by primary and secondary injuries. The former is irreversible physical injury to the spine, whereas the latter is a series of chemical, reversible secondary pathophysiological changes including neuro-inflammatory response, neuronal apoptosis, and oxidative stress, worsening neurologic recovery [2,3,4]. Secondary injury is reversible and can be controlled.
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