In Vivo Gene Delivery of STC2 Promotes Axon Regeneration in Sciatic Nerves

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 that Stc2 is immediately upregulated after axotomy. Stc2 is required for axon regeneration in vivo and in vitro, indicating that Stc2 is a neuronal factor regulating axonal injury response. The application of the secreted stanniocalcin 2 to injured DRG neurons promotes regeneration. Stc2 thus represents a potential secretory protein with a feedback function regulating regeneration. Finally, the in vivo gene delivery of STC2 increases regenerative growth after injury in peripheral nerves in mice. These results suggest that Stc2 is an injury-responsive gene required for axon regeneration and a potential target for developing therapeutic applications.