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J Cell Mol Med ; 27(23): 3706-3716, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37950418

RESUMO

Excessive productions of inflammatory cytokines and free radicals are involved in spinal cord injury (SCI). Fibroblast growth factor 5 (FGF5) is associated with inflammatory response and oxidative damage, and we herein intend to determine its function in SCI. Lentivirus was instilled to overexpress or knockdown FGF5 expression in mice. Compound C or H89 2HCl were used to suppress AMP-activated protein kinase (AMPK) or protein kinase A (PKA), respectively. FGF5 level was significantly decreased during SCI. FGF5 overexpression mitigated, while FGF5 silence further facilitated inflammatory response, oxidative damage and SCI. Mechanically, FGF5 activated AMPK to attenuate SCI in a cAMP/PKA-dependent manner, while inhibiting AMPK or PKA with pharmacological methods significantly abolished the neuroprotective effects of FGF5 against SCI. More importantly, serum FGF5 level was decreased in SCI patients, and elevated serum FGF5 level often indicate better prognosis. Our study identifies FGF5 as an effective therapeutic and prognostic target for SCI.


Assuntos
Proteínas Quinases Ativadas por AMP , Fator 5 de Crescimento de Fibroblastos , Estresse Oxidativo , Traumatismos da Medula Espinal , Animais , Humanos , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Fator 5 de Crescimento de Fibroblastos/genética , Fator 5 de Crescimento de Fibroblastos/metabolismo , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Camundongos Knockout , Masculino , Feminino , Adulto , Pessoa de Meia-Idade
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