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Updated: Aug 11, 2026
Promotion of Survival and Differentiation of Neural Stem Cells with Fibrin and Growth Factor Cocktails after Severe Spinal Cord Injury
Published on: July 27, 2014
FGF-18 Protects the Injured Spinal cord in mice by Suppressing Pyroptosis and Promoting Autophagy via the
Feida Li1,2,3, Tingwen Cai1,2,3, Letian Yu4
1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 325027, Wenzhou, China.
Abstract:
Spinal cord injury (SCI) is a severe medical condition with lasting effects. The efficacy of numerous clinical treatments is hampered by the intricate pathophysiological mechanism of SCI. Fibroblast growth factor 18 (FGF-18) has been found to exert neuroprotective effects after brain ischaemia, but its effect after SCI has not been well explored. The aim of the present study was to explore the therapeutic effect of FGF-18 on SCI and the related mechanism. In the present study, a mouse model of SCI was used, and the results showed 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 increased autophagy, and the well-known autophagy inhibitor 3-methyladenine (3MA) reversed the therapeutic benefits of FGF-18 after SCI, suggesting that autophagy mediates the therapeutic effects of FGF-18 on SCI. A mechanistic study revealed that after stimulation of the protein kinase B (AKT)-transient receptor potential mucolipin 1 (TRPML1)-calcineurin signalling pathway, the FGF-18-induced increase in autophagy was mediated by the dephosphorylation and nuclear translocation of transcription factor E3 (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 SCI in the clinic.
Insights
Fibroblast growth factor 18 (FGF-18) enhances functional recovery after spinal cord injury (SCI) by boosting autophagy and reducing pyroptosis. This suggests FGF-18 is a promising therapeutic agent for SCI treatment.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Cellular Biology
Background:
- Spinal cord injury (SCI) presents significant challenges to treatment due to complex pathophysiology.
- Fibroblast growth factor 18 (FGF-18) shows neuroprotection in brain ischemia, but its role in SCI is understudied.
Purpose of the Study:
- To investigate the therapeutic potential of FGF-18 in a mouse model of SCI.
- To elucidate the underlying mechanisms of FGF-18's effects on SCI recovery.
Main Methods:
- Utilized a mouse model of spinal cord injury.
- Administered FGF-18 and assessed functional recovery.
- Investigated the roles of autophagy and pyroptosis.
- Employed the autophagy inhibitor 3-methyladenine (3MA).
- Analyzed the AKT-TRPML1-calcineurin-TFE3 signaling pathway.
Main Results:
- FGF-18 significantly improved functional recovery in SCI mice.
- FGF-18 treatment increased autophagy and decreased pyroptosis.
- Autophagy inhibition by 3MA reversed the beneficial effects of FGF-18.
- FGF-18-induced autophagy is mediated by the AKT-TRPML1-calcineurin pathway, leading to TFE3 dephosphorylation and nuclear translocation.
Conclusions:
- FGF-18 acts as a potent autophagy modulator, accelerating functional recovery post-SCI.
- The mechanism involves enhancing autophagy via the AKT-TRPML1-calcineurin-TFE3 pathway.
- FGF-18 represents a potential novel therapeutic strategy for clinical application in spinal cord injury.
