Fibroblast Growth Factor 22 Inhibits ER Stress-Induced Apoptosis and Improves Recovery of Spinal Cord Injury

Frontiers in Pharmacology, 2020 · DOI: 10.3389/fphar.2020.00018 · Published: February 11, 2020

Spinal Cord Injury Pharmacology Genetics

Simple Explanation

Spinal cord injury (SCI) often leads to permanent motor dysfunction due to limited regeneration in humans. The injury causes neuronal apoptosis, autophagy, vascular dysfunction, oxidative stress and inflammation, leading to tissue damage. The endoplasmic reticulum (ER) maintains cellular homeostasis and resists injury from misfolded proteins. During SCI, protein misfolding leads to the unfolded protein response (UPR), activating apoptotic proteins and neuronal death. This study shows that FGF22 can inhibit neuronal apoptosis induced by ER stress and promote SCI recovery. FGF22 administration promoted recovery and increased neuron survival in the spinal cord lesions of model mice.

Study Duration

60 Days

Participants

Eighty adult female SD rats (weighing 220–250 g)

Evidence Level

Not specified

Key Findings

1
FGF22 administration promoted recovery and increased neuron survival in the spinal cord lesions of model mice. The protective effect of FGF22 is related to decreased expression of CHOP, GRP78, caspase-12, XBP1, Eif-2a and Bad which are ER stress-induced apoptosis response proteins.
2
FGF22 administration also increased the number of neurons and the expression of growth-associated protein 43 (GAP43) which was related to axon regeneration.
3
The study illustrated that the function of FGF22 is related to the inhibition of ER stress-induced cell death in SCI recovery via activation of downstream signals.

Research Summary

This study investigated the mechanism of ER stress-induced apoptosis and the protective action of fibroblast growth factor 22 (FGF22) in vivo in a rat model of spinal cord injury (SCI). The results demonstrated that ER stress-induced apoptosis plays a significant role in injury of SCI model rats and that FGF22 administration promoted recovery and increased neuron survival in the spinal cord lesions. The protective effect of FGF22 effectively reduces neuronal apoptosis and promotes axonal regeneration, suggesting a new tendency of FGF22 therapy development in central neural system injuries involving chronic ER stress-induced apoptosis.

Practical Implications

Therapeutic Potential

FGF22 could be a potential therapeutic agent for spinal cord injury due to its ability to inhibit ER stress-induced apoptosis and promote axonal regeneration.

Targeted Drug Development

Further research into the mechanisms by which FGF22 inhibits ER stress could lead to the development of more targeted and effective treatments for SCI.

Clinical Applications

The findings suggest a new avenue for FGF22 therapy development in central neural system injuries, particularly those involving chronic ER stress-induced apoptosis.

Study Limitations

1
The study was conducted on rats, and further research is needed to determine if the findings are applicable to humans.
2
Further prove that FGF22 indeed functions through the ER stress pathways to promote SCI recovery, we will use Chop knockout SD rats and further verify our experimental results.
3
Not specified

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