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  3. Recombinant fibroblast growth factor 4 ameliorates axonal regeneration and functional recovery in acute spinal cord injury through altering microglia/macrophage phenotype

Recombinant fibroblast growth factor 4 ameliorates axonal regeneration and functional recovery in acute spinal cord injury through altering microglia/macrophage phenotype

  • Int Immunopharmacol. 2024 Jun 15:134:112188. doi: 10.1016/j.intimp.2024.112188.
Rui Li 1,  Juerong Feng 2,  Liuxun Li 2,  Guotian Luo 2,  Yongpeng Shi 2,  Shichao Shen 2,  Xinrong Yuan 2,  Jianlong Wu 2,  Bin Yan 3,  Lei Yang 4
Affiliations

Affiliations

  • 1 Orthopaedics/Department of Spine Surgery, Department of Pharmacy and Department of Gastroenterology, Shenzhen Second People's Hospital (Shenzhen Institute of Translational Medicine), Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China; State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
  • 2 Orthopaedics/Department of Spine Surgery, Department of Pharmacy and Department of Gastroenterology, Shenzhen Second People's Hospital (Shenzhen Institute of Translational Medicine), Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China.
  • 3 Orthopaedics/Department of Spine Surgery, Department of Pharmacy and Department of Gastroenterology, Shenzhen Second People's Hospital (Shenzhen Institute of Translational Medicine), Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China. Electronic address: yanbinzhiyou@163.com.
  • 4 Orthopaedics/Department of Spine Surgery, Department of Pharmacy and Department of Gastroenterology, Shenzhen Second People's Hospital (Shenzhen Institute of Translational Medicine), Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China. Electronic address: yangl@email.szu.edu.cn.
PMID: 38728880 DOI: 10.1016/j.intimp.2024.112188
Abstract

Neuroinflammation is one of the extensive secondary injury processes that aggravate metabolic and cellular dysfunction and tissue loss following spinal cord injury (SCI). Thus, an anti-inflammatory strategy is crucial for modulating structural and functional restoration during the stage of acute and chronic SCI. Recombinant Fibroblast Growth Factor 4 (rFGF4) has eliminated its mitogenic activity and demonstrated a metabolic regulator for alleviating hyperglycemia in type 2 diabetes and liver injury in non-alcoholic steatohepatitis. However, it remains to be explored whether or not rFGF4 has a neuroprotective effect for restoring neurological disorders, such as SCI. Here, we identified that rFGF4 could polarize microglia/macrophages into the restorative M2 subtype, thus exerting an anti-inflammatory effect to promote neurological functional recovery and nerve fiber regeneration after SCI. Importantly, these effects by rFGF4 were related to triggering PI3K/Akt/GSK3β and attenuating TLR4/NF-κB signaling axes. Conversely, gene silencing of the PI3K/Akt/GSK3β signaling or pharmacological reactivation of the TLR4/NF-κB axis aggravated inflammatory reaction. Thus, our findings highlight rFGF4 as a potentially therapeutic regulator for repairing SCI, and its outstanding effect is associated with regulating macrophage/microglial polarization.

Keywords

Microglia/macrophage polarization; Neuroinflammation; Neuroprotection; Recombinant fibroblast growth factor 4 (rFGF4); Spinal cord injury (SCI).

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