2022, Vol. 26 ›› Issue (20): 3220-3224

Interaction of Nogo-A/NgR signaling pathway and NGF/TrkA signaling pathway during the regeneration of injured spinal cord nerve axons

Yang Lin1, Wu Yao1, Zhou Binbin2   

Abstract: BACKGROUND: Growth-associated protein 43, as a membrane-like phosphoprotein, is a marker protein of neuronal regeneration plasticity and participates in the key process of axonal regeneration and the connection of various stages. It is of great significance for central nerve regeneration.
OBJECTIVE: To investigate the mechanism of nerve regeneration and recovery after spinal cord injury by observing the interaction of neurite outgrowth inhibitor A (Nogo-A)/neurite growth inhibitor receptor (NgR) signaling pathway and nerve growth factor (NGF)/tyrosine kinase (TrkA) signaling pathway on the expression of growth-associated protein 43.
METHODS: A total of 120 Sprague-Dawley rats were randomly divided into 5 groups: NgR blocking group, TrkA blocking group, double blocking agent group, injury control group, and sham surgery group. Rats in the sham surgery group underwent laminectomy (without injury to the spinal cord); and spinal cord injury rat models were established in the other groups. Immediately after successful modeling, rats in the NgR blocking group were injected with 25 μL of NEP1-40, a NgR blocker, and 25 μL of normal saline in the injured segment. Rats in the TrkA blocking group were injected with 25 μL of K252a, a TrkA blocker, and 25 μL of normal saline. Rats in the double blocking agent group were injected with 25 μL of NEP1-40 and 25 μL of K252a. Rats in the injury control group and the sham surgery group were injected with 50 μL of normal saline. On the 3rd, 7th, 14th, and 21st days after the intervention, the mRNA and protein expression of growth-associated protein 43 in rat spinal cord tissue were detected by immunohistochemistry, PCR, and western blot.
RESULTS AND CONCLUSION: The results of immunohistochemistry, PCR, and western blot showed that the mRNA and protein expression of growth-associated protein 43 in the NgR blocking group, the TrkA blocking group, the double blocking agent group and the injury control group was higher than that in the sham surgery group. The expression of growth-associated protein 43 in the NgR blocking group and the double blocking agent group was higher than that in the injury control group, and there was a significant difference on the 7th and 14th days (P < 0.05 or P < 0.01). The mRNA and protein expression of growth-associated protein 43 in the TrkA blocking group was lower than that in the injury control group, and the difference was significant on the 7th and 14th days (P < 0.05 or P < 0.01). To conclude, the results from the NgR blocking group proves that the Nogo-A/NgR signaling pathway can significantly increase the expression of growth-associated protein 43 and promote the regeneration of nerve axons. The results from the TrkA blocking group proves that the NGF/TrkA signaling pathway can reduce the expression of growth-associated protein 43 and inhibit the regeneration of nerve axons. The results from the double blocking agent group shows that the interaction of the Nogo-A/NgR signaling pathway and the NGF/TrkA signaling pathway can promote the expression of growth-associated protein 43.
Key words: nerve regeneration, Nogo-A/NgR signaling pathway, NGF/TrkA signaling pathway, interaction