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

EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2023 · DOI: 10.3892/etm.2023.12039 · Published: March 24, 2023

Simple Explanation

This study investigates the role of Fibroblast Growth Factor 23 (FGF23) in spinal cord injury (SCI). FGF23 is known to regulate neuronal morphology, synaptic growth, and inflammation. The research uses both in vitro (primary rat neurons stimulated with H2O2) and in vivo (SCI rat model) models to examine how FGF23 affects neuronal apoptosis, inflammation, and locomotion recovery. The study also explores the underlying mechanism, focusing on the PI3K/AKT signaling pathway, and tests whether inhibiting this pathway can reverse the effects of FGF23.

Study Duration

28 days

Participants

60 male Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
FGF23 overexpression decreased cell apoptosis and inflammation in H2O2-stimulated neurons by activating the PI3K/AKT signaling pathway.
2
In SCI model rats, FGF23 overexpression reduced tissue laceration and inflammatory cell infiltration, decreased TNF-α and IL-1β levels, and improved locomotion recovery.
3
Inhibition of the PI3K/AKT pathway reversed the positive effects of FGF23, indicating that FGF23's benefits are mediated through this pathway.

Research Summary

This 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. 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). FGF23 alleviated neuronal apoptosis and inflammation, and promoted locomotion recovery via activation of PI3K/AKT signalling in SCI, indicating its potential as a treatment option for SCI; however, further studies are warranted for validation.

Practical Implications

Potential Therapeutic Target

FGF23 may serve as a potential therapeutic target for spinal cord injury due to its ability to reduce neuronal apoptosis and inflammation, and promote locomotion recovery.

PI3K/AKT Pathway Activation

Activating the PI3K/AKT signaling pathway may be a viable strategy to mitigate the effects of spinal cord injury, given FGF23's mechanism of action.

Further Research Needed

Further studies are needed to validate FGF23 as a treatment option for SCI and to fully elucidate the underlying mechanism of its regulatory role in the PI3K/AKT signaling pathway.

Study Limitations

1
The underlying mechanism of the regulatory role of FGF23 in PI3K/AKT signalling still requires further investigation.
2
Inflammatory cytokines were only detected in vivo but not in vitro; the reason for this issue was that the primary neurons used in the in vitro study were collected from the cerebral cortex of the foetal rat, which did not secrete inflammatory cytokines.
3
the effect of LY294002 monotherapy on SCI rats was not assessed in vivo. The reason for this was that the effect of LY294002 in SCI model rats had already been assessed in the previous studies (19,22), hence, the current study did not re‑assess this documented issue.

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