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

Abstract

Currently, inhibiting or reducing neuronal cell death is the main strategy to improve recovery of spinal cord injury (SCI). Therapies using nerve growth factors to treat SCI mainly focused on reducing the area damaged by postinjury degeneration to promote functional recovery. In this report, we investigated the mechanism of ER (endoplasmic reticulum) stress-induced apoptosis and the protective action of fibroblast growth factor 22 (FGF22) in vivo. Our results demonstrated that ER stress-induced apoptosis plays a significant role in injury of SCI model rats. 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 (C/EBP-homologous protein), GRP78 (glucose-regulated protein 78), caspase-12, X-box binding protein 1 (XBP1), eukaryotic initiation factor 2a (Eif-2a) and Bad which are ER stress-induced apoptosis response proteins. Moreover, FGF22 administration also increased the number of neurons and the expression of growth-associated protein 43 (GAP43) which was related to axon regeneration. We also demonstrated that the protective effect of FGF22 effectively reduces neuronal apoptosis and promotes axonal regeneration. Our study first 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. This study also suggested a new tendency of FGF22 therapy development in central neural system injuries, which involved chronic ER stress-induced apoptosis.

Blood DNA Methylation Predicts Diabetic Kidney Disease Progression in High Fat Diet-Fed Mice

“…Multiple FGFs have been shown to be elevated in patients with chronic kidney disease, including FGF21 and FGF23 [46,47]. The implication of FGF22 has not yet been elucidated; however, mice treated with FGF22 demonstrated reduced pro-apoptosis proteins and increased recovery of spinal cord injury, suggesting tissue protective effects [48].…”

Protein disulfide isomerase A6 promotes the repair of injured nerve through interactions with spastin

“…The damage associated with SCI can be extremely severe, resulting in substantial functional impairment including permanent motor dysfunction in affected patients owing to the limited regenerative responses engaged in humans following such injury ( Zhu et al, 2020 ; Bisicchia et al, 2022 ). The pathogenesis of SCI is linked to mechanisms that govern both primary and secondary injury ( Walsh et al, 2021 ; Ding and Chen, 2022 ), with secondary damage in particular contributing to more widespread neuronal death, expanding the affected region of the spinal cord ( Lai et al, 2021 ).…”

Catalpol as a Component of Rehmannia glutinosa Protects Spinal Cord Injury by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis

“…In the footprint test, the rats' hind paws were dipped with red dye to have the locomotor function analyzed as previously described (de Medinaceli et al, 1982). The following parameters were applied to evaluate locomotion function: 1) weight support, 2) leg extensor spasms, 3) the number of footsteps, and 4) the posture of the foot (Zhu et al, 2020a).…”