Down-regulation of PGAM5 attenuates spinal cord injury-induced neuronal injury by inhibiting ASK-1/p38/NF-kB signaling.

Introduction: The morbidity and mortality of spinal cord injury (SCI) are increasing year by year. It is of vital importance to ascertain the mechanism of SCI. Phosphoglycerate mutase family member 5 (PGAM5) is viewed as a molecular marker of SCI, but its specific role in SCI is elusive.

Material and methods: Following establishment of the SCI mouse model, the pathological examination of the spinal cord was initially assessed using H&E staining. PGAM5 expression in spinal cord tissues was appraised utilizing immunohistochemistry and RT-qPCR. Subsequently, after the expression of PGAM5 in SCI mice was inhibited by adenovirus transfection, the degree of SCI was determined, and the motor ability of hind limbs was estimated with the BBB score. In addition, the apoptosis of neurons, microglia activation and the generation of inflammatory cytokines in the spinal cord of mice were detected. Next, at the cellular level, PGAM5 expression was inhibited in the BV2 microglial cells induced by lipopolysaccharide (LPS), so as to explore the effects of down-regulation of PGAM5 on the activation, inflammation and apoptosis of neurons. Finally, western blot was applied for the appraisement of apoptosis signal-regulating kinase-1 (ASK-1)/p38/nuclear factor-kappa B (NF-kB) signaling-associated proteins.

Results: PGAM5 expression in SCI mice was found to be raised. Inhibition of PGAM5 expression in SCI mice can significantly reduce spinal cord pathological injury, SCI-induced neuronal apoptosis, microglial cell activation and inflammation. The above regulatory process might be realized through the ASK-1/p38/NF-kB signaling pathway mediated by PGAM5.

Conclusions: Down-regulation of PGAM5 attenuated SCI-induced neuronal injury by inhibiting ASK-1/p38/NF-kB signaling.