In Vivo Gene Delivery ofSTC2Promotes Axon Regeneration in Sciatic Nerves

Abstract

Neurons are vulnerable to injury, and failure to activate self-protective systems after injury leads to neuronal death. However, sensory neurons in dorsal root ganglions (DRGs) mostly survive and regenerate their axons. To understand the mechanisms of the neuronal injury response, we analyzed the injury-responsive transcriptome and found thatStc2is immediately upregulated after axotomy.Stc2is required for axon regeneration in vivo and in vitro, indicating thatStc2is a neuronal factor regulating axonal injury response. The application of the secreted stanniocalcin 2 to injured DRG neurons promotes regeneration.Stc2thus represents a potential secretory protein with a feedback function regulating regeneration. Finally, the in vivo gene delivery ofSTC2increases regenerative growth after injury in peripheral nerves in mice. These results suggest thatStc2is an injury-responsive gene required for axon regeneration and a potential target for developing therapeutic applications.