FGF1 improves functional recovery through inducing PRDX1 to regulate autophagy and anti‐ROS after spinal cord injury

Abstract

Fibroblast growth factor 1 (FGF1) is thought to exert protective and regenerative effects on neurons following spinal cord injury (SCI), although the mechanism of these effects is not well understood. The use of FGF1 as a therapeutic agent is limited by its lack of physicochemical stability and its limited capacity to cross the blood‐spinal cord barrier. Here, we demonstrated that overexpression of FGF1 in spinal cord following SCI significantly reduced tissue loss, protected neurons in the ventricornu, ameliorated pathological morphology of the lesion, dramatically improved tissue recovery via neuroprotection, and promoted axonal regeneration and remyelination both in vivo and in vivo. In addition, the autophagy and the expression levels of PRDX1 (an antioxidant protein) were induced by AAV‐FGF1 in PC12 cells after H2O2 treatment. Furthermore, the autophagy levels were not changed in PRDX1‐suppressing cells that were treated by AAV‐FGF1. Taken together, these results suggest that FGF1 improves functional recovery mainly through inducing PRDX1 expression to increase autophagy and anti‐ROS activity after SCI.

Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair

“…Therefore, combinatorial growth factors (GFs), including acidic fibroblast growth factor (aFGF) and brain-derived neurotrophic factor (BDNF), which can target different types of cells in the injured spinal cord, were used here. aFGF plays an essential role in adjusting synaptic plasticity through various cellular mechanisms, as shown in our previous studies 24 , 25 , and BDNF regulates key processes in neuronal survival and plasticity 26 , 27 . These effects are complementary to those of DTX, making GFs promising and excellent candidates for the combined treatment of SCI.…”

“…For in vitro Tuj-1, ace-tubulin, tyr-tubulin, and growth cone staining, neurons were placed on coverslips in 12-well plates and treated as described above. After treatment, the cells were fixed in 4% paraformaldehyde and permeabilized in PHEM buffer (60 mM PIPES, 25 mM HEPES, 5 mM EGTA, and 1 mM MgCl), as previously described 24 , for immunofluorescence staining. For assessment of in vivo immunofluorescence, spinal cords were collected and post-fixed in 4% paraformaldehyde at 4°C overnight, dehydrated in alcohol, and then paraffin embedded.…”

Acidic Fibroblast Growth Factor in Spinal Cord Injury

“…Hence, it is expected that aFGF probably play some roles in the repair of nerve injury, both in peripheral and in CNSs. 53…”

Nanoparticle-Based Systems for Delivery of Protein Therapeutics to the Spinal Cord

“…A 2015 study found that co-expression of IGF1 and osteopontin (OPN) could promote axon regeneration in retinal ganglion cells ( Duan et al, 2015 ; He and Jin, 2016 ). It has also been shown that overexpression of fibroblast growth factor 1 (FGF-1) in the spinal cord improves functional recovery after SCI, as measured by the Basso-Beattie-Bresnahan locomotion scale ( Li et al, 2018 ). Liraglutide, a glucagon-like peptide 1 analog that is already an approved treatment for type 2 diabetes, has similarly been implicated in functional recovery ( Chen et al, 2017 ).…”

“…Thus, the question becomes whether such protein therapeutics can be reliably delivered to the spinal cord. Studies have successfully delivered protein therapeutics, and seen associated functional improvements, through implantation of adeno-associated virus (AAV) vectors into the spinal cord ( Li et al, 2018 ). These findings are very promising in terms of their potential applications to patients in the short-term future.…”