Therapeutic Potential of Growth Hormone in Peripheral Nerve Injury: Enhancing Schwann Cell Proliferation and Migration Through IGF‐1R‐AKT and ERK Signaling Pathways

ABSTRACT Peripheral nerve injury (PNI) represents a prevalent condition characterized by the demyelination of affected nerves. The challenge of remyelinating these nerves and achieving satisfactory functional recovery has long been a persistent issue. The specific contributions of growth hormone (GH) in the aftermath of PNI have remained ambiguous. Our investigations have demonstrated that GH not only enhances neurological function scores but also promotes remyelination within a three‐week period. Further in vivo studies corroborated that GH facilitates nerve function improvement by mitigating neuronal apoptosis. In vitro, the ideal concentration of GH for exerting effects on Schwann cells (SCs) has been identified as 80 ng/mL. Subsequent research uncovered GH's profound impact on SCs proliferation, cell cycle progression, and migration. Through RNA sequencing and additional experiments, it was discovered that GH treatment elevates the phosphorylation levels of IGF‐1R, AKT, and ERK. Moreover, the GH‐induced proliferation and migration of SCs were significantly diminished by the inhibition of the IGF‐1R pathway, achieved through pre‐treatment with Linsitinib. The outcomes of this investigation suggest that GH can significantly enhance the proliferation and migration of SCs, presenting it as a viable option for PNI repair.