Overexpression of c-Jun inhibits erastin-induced ferroptosis in Schwann cells and promotes repair of facial nerve function.

Myelin undergoes various changes after nerve injury, and c-Jun has a close relationship with Schwann cells (SCs). However, it remains unclear whether c-Jun can be involved in nerve repair by regulating ferroptosis. To explore this, we first set up a facial nerve injury model and detected the changes of ferroptosis-related proteins and c-Jun by immunofluorescence and Western blot. Then, we cultured RSC 96 and pSCs, and studied the potential regulatory relationships by a combination of experimental methods such as CCK-8, ELISA, immunofluorescence, qRT-PCR, Western blot and viral transfection. Finally, we corroborated the role of c-Jun through animal experiments. Our experiments revealed that ferroptosis occurs after facial nerve injury. Erastin decreased GPX4, c-Jun proteins and GSH content, while PTGS2, NRF2, HO-1 proteins, MDA, Fe2+ and ROS contents increased. This effect was inhibited after c-Jun overexpression but was reversed after the addition of c-Jun siRNA. Besides, we proved in vivo that c-Jun could inhibit ferroptosis and promote the recovery of facial nerve function. In conclusion, our study identified the relationship between c-Jun and ferroptosis during peripheral nerve injury repair, which provides new ideas for studying peripheral nerve injury and repair.