The GDF11 Promotes Nerve Regeneration After Sciatic Nerve Injury in Adult Rats by Promoting Axon Growth and Inhibiting Neuronal Apoptosis

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.

The Effect of Liraglutide on Axon Regeneration and Functional Recovery after Peripheral Nerve Lesion

“…Due to the anti-inflammatory effects of GDF-11, it has been studied exogenously in experimental studies in processes such as fatty liver, renal injury, spinal cord injury, peripheral nerve injury, and cerebral hemorrhage, and positive results have been found regarding its protective and healing effects [40][41][42]. Previous research has demonstrated that GDF-11 can impede cell apoptosis [43], facilitate the growth of axons and synapses [44,45], and initiate neuronal regeneration.…”

Identification of immunodiagnostic blood biomarkers associated with spinal cord injury severity

“…In SCI, GDF11 protects the injured spinal cord by inhibiting pyroptosis and necroptosis through TFE3-mediated enhancement of autophagy ( 41 ). GDF11 also promotes nerve regeneration after sciatic nerve injury in adult rats by promoting axonal growth and inhibiting neuronal apoptosis ( 42 ). However, there is no research on the specific mechanism of GDF11 in the immune response to SCI.…”

Tissue Expression of Growth Differentiation Factor 11 in Patients with Breast Cancer

“…Since it was first discovered in 1999, GDF11 has been shown to be involved in normal physiological processes including erythropoiesis and embryonic development [12]. Moreover, GDF11 has been implicated in the pathophysiology of tumor growth [13][14][15], organ development [16], aging [17,18], and the nervous system [19]. GDF11 has been shown to exhibit powerful physiological functions; however, controversy exists regarding its role in cancer biology.…”