Affiliation:
1. Wenzhou Medical University
Abstract
Abstract
Spinal cord injury (SCI) refers to a severe medical condition with lasting effects. The efficacy of numerous clinical treatments is hampered by its intricate pathophysiological mechanism. FGF-18 has been found to exert neuroprotective effects after brain ischaemia, while its effect after SCI has not been well explored. In the present study, we used a mice model of SCI and found that FGF-18 may significantly affect functional recovery. The present findings demonstrated that FGF-18 directly promoted functional recovery by increasing autophagy and decreasing pyroptosis. In addition, FGF-18 upregulated autophagy, and the well-known autophagy inhibitor, 3-methyladenine (3MA), reversed the therapeutic benefits of FGF-18 on SCI, suggesting that autophagy mediates the therapeutic benefits of FGF-18 on SCI. After stimulation of the AKT-TRPML1-calcineurin signalling pathway, mechanistic analysis revealed that the FGF-18-induced increase in autophagy was mediated by the dephosphorylation and nuclear translocation of TFE3. Together, these findings indicated that FGF-18 is a robust autophagy modulator capable of accelerating functional recovery after SCI, suggesting that it may be a promising treatment for application in the clinic.
Publisher
Research Square Platform LLC