Abstract
Introduction: Sciatic nerve injury is a common injury of the nervous system. Stem cell-based therapies, drug-based therapies and rehabilitation physiotherapy therapies are currently available, but their limited therapeutic efficacy limits their use. Here, we aimed to explore a novel lentiviral-based gene therapeutic strategy and to elaborate its mechanism. Materials and Methods: Recombinant GDF11 protein was used for the in vitro treatment of dorsal root ganglion (DRG) cells. Lentivirus was used to construct a vector system for the in vivo expression of GDF11. The nerve conduction function was detected using action-evoked potentials at different time periods, and the regulatory effect of nerves on target organs was detected by weighing the gastrocnemius muscle. Immunofluorescence of NF200 and S100 was used to show the regeneration of the sciatic nerve, and myelin and Nissl staining were performed to observe the pathological features of the tissue. Western was used to validate signaling pathways. The expression of related genes was observed by qPCR and Western blotting, and cell apoptosis was detected by flow cytometry. Result: GDF11 promotes the axonal growth of DRG cells and inhibits DGR cell apoptosis in vitro. GDF11 acts by activating the Smad pathway. GDF11 promotes the recovery of damaged sciatic nerve function in rats, the regeneration of damaged sciatic nerves in rats, and myelin regeneration of damaged sciatic nerves in rats. GDF11 also exerts a protective effect on neuronal cells in rats. Conclusion: Based on the present study, we conclude that GDF11 promotes axonal growth and inhibits DRG cell apoptosis in vitro through the Smad pathway, and lentivirus-mediated GDF11 overexpression in vivo can promote the recovery of sciatic nerves after transection by promoting axonal growth and inhibiting neuronal apoptosis in the spinal cord.
Highlights
Sciatic nerve injury is a common injury of the nervous system
To investigate the influence of GDF11 on neuronal cells, Dorsal Root Ganglion (DRG) cells were isolated from rats and cultured with neuronal selective medium to simulate the effect of GDF11 on neuronal cells in vitro
Basic cell apoptosis occurred under normal culture conditions, whereas the apoptotic rate of the cells cultured with GDF11 was significantly decreased (Figures 2A,B)
Summary
Sciatic nerve injury is a common injury of the nervous system. Stem cellbased therapies, drug-based therapies and rehabilitation physiotherapy therapies are currently available, but their limited therapeutic efficacy limits their use. The specific molecular mechanism of sciatic nerve degeneration and regeneration is not very clear, it is generally believed that this is a complex series of events, which includes local macrophage activation after injury, the attraction of circulating immune cells participating in necrosis (Shi et al, 2018; Fan et al, 2019; Kalinski et al, 2020) and neural axon degeneration and atrophy (Yu et al, 2018) due to an abnormal neuronal cell body leads to increased Schwann cell apoptosis increased (Jia et al, 2020; Yardim et al, 2021), the demyelination of nerve fibers and the local proliferation of fibroblasts to induce scar formation (Que et al, 2013). The body will gradually adjust to these adverse factors such that the injured nerve slowly undergoes incomplete repair
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