Lentivirus-mediated knockdown of Ski inhibits glial scar formation and promotes axonal regeneration and functional recovery after spinal cord injury in rats

Abstract

The glial scar that forms at the site of injury after spinal cord injury (SCI) is an important physical and biochemical barrier that prevents axonal regeneration and thus delays functional recovery. Ski is a multifunctional transcriptional co-regulator that is involved in a wide range of physiological and pathological processes in humans. Previous studies by our group found that Ski is significantly upregulated in the spinal cord after in vivo injury and in astrocytes after in vitro activation, suggesting that Ski may be a novel molecule regulating astrocyte activation after spinal cord injury. Further studies revealed that knockdown or overexpression intervention of Ski expression could significantly affect the proliferation and migration of activated astrocytes. To further verify the effect of knockdown of Ski expression in vivo on glial scar formation and functional recovery after spinal cord injury, we prepared a rat spinal cord injury model using Allen's percussion method and used lentivirus as a vector to mediate the downregulation of Ski in the injured spinal cord. The results showed that knockdown of Ski expression after spinal cord injury significantly inhibited the expression of Glial Fibrillary Acidic Protein (Gfap) and Vimentin, the hallmark molecules of glial scar, and increased the expression of Neurofilament-200 (Nf-200), a key molecule for axonal regeneration, and Synaptophysin, a key molecule for synapse formation. In addition, knockdown of Ski after spinal cord injury also promoted the recovery of motor function. Taken together, these results demonstrate that Ski is an important regulator of glial scar formation at the injury site and promotes axonal regeneration and synapse formation after spinal cord injury, and is a potential target for targeted therapy after spinal cord injury.