FGF23 alleviates neuronal apoptosis and inflammation, and promotes locomotion recovery via activation of PI3K/AKT signalling in spinal cord injury.

Abstract

Fibroblast growth factor 23 (FGF23) regulates neuronal morphology, synaptic growth and inflammation; however, its involvement in spinal cord injury (SCI) remains unclear. Therefore, the present study aimed to investigate the effect of FGF23 on neuronal apoptosis, inflammation and locomotion recovery, as well as its underlying mechanism in experimental SCI models. Primary rat neurons were stimulated with H2O2 to establish an in vitro model of SCI and were then transfected with an FGF23 overexpression (oeFGF23) or short hairpin RNA (shFGF23) adenovirus-associated virus and treated with or without LY294002 (a PI3K/AKT inhibitor). Subsequently, an SCI rat model was constructed, followed by treatment with oeFGF23, LY294002 or a combination of the two. FGF23 overexpression (oeFGF23 vs. oeNC) decreased the cell apoptotic rate and cleaved-caspase3 expression, but increased Bcl-2 expression in H2O2-stimulated neurons, whereas shFGF23 transfection (shFGF23 vs. shNC) exhibited the opposite effect (all P<0.05). Furthermore, FGF23 overexpression (oeFGF23 vs. oeNC) could activate the PI3K/AKT signalling pathway, whereas treatment with the PI3K/AKT inhibitor (LY294002) (oeFGF23 + LY294002 vs. LY294002) attenuated these effects in H2O2-stimulated neurons (all P<0.05). In SCI model rats, FGF23 overexpression (oeFGF23 vs. oeNC) reduced the laceration and inflammatory cell infiltration in injured tissue, decreased TNF-α and IL-1β levels, and improved locomotion recovery (all P<0.05); these effects were attenuated by additional administration of LY294002 (oeFGF23 + LY294002 vs. LY294002) (all P<0.05). In conclusion, FGF23 alleviated neuronal apoptosis and inflammation, and promoted locomotion recovery via activation of the PI3K/AKT signalling pathway in SCI, indicating its potential as a treatment option for SCI; however, further studies are warranted for validation.