Therapeutic application of nicotinamide: As a potential target for inhibiting fibrotic scar formation following spinal cord injury.
CNS Neurosci Ther
; 30(7): e14826, 2024 Jul.
Article
de En
| MEDLINE
| ID: mdl-38973179
ABSTRACT
AIM:
We aimed to confirm the inhibitory effect of nicotinamide on fibrotic scar formation following spinal cord injury in mice using functional metabolomics.METHODS:
We proposed a novel functional metabolomics strategy to establish correlations between gene expression changes and metabolic phenotypes using integrated multi-omics analysis. Through the integration of quantitative metabolites analysis and assessments of differential gene expression, we identified nicotinamide as a functional metabolite capable of inhibiting fibrotic scar formation and confirmed the effect in vivo using a mouse model of spinal cord injury. Furthermore, to mimic fibrosis models in vitro, primary mouse embryonic fibroblasts and spinal cord fibroblasts were stimulated by TGFß, and the influence of nicotinamide on TGFß-induced fibrosis-associated genes and its underlying mechanism were examined.RESULTS:
Administration of nicotinamide led to a reduction in fibrotic lesion area and promoted functional rehabilitation following spinal cord injury. Nicotinamide effectively downregulated the expression of fibrosis genes, including Col1α1, Vimentin, Col4α1, Col1α2, Fn1, and Acta2, by repressing the TGFß/SMADs pathway.CONCLUSION:
Our functional metabolomics strategy identified nicotinamide as a metabolite with the potential to inhibit fibrotic scar formation following SCI by suppressing the TGFß/SMADs signaling. This finding provides new therapeutic strategies and new ideas for clinical treatment.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Traumatismes de la moelle épinière
/
Fibrose
/
Cicatrice
/
Nicotinamide
/
Souris de lignée C57BL
Limites:
Animals
Langue:
En
Journal:
CNS Neurosci Ther
Sujet du journal:
NEUROLOGIA
/
TERAPEUTICA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine