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

Abstract

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.