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Therapeutic application of nicotinamide: As a potential target for inhibiting fibrotic scar formation following spinal cord injury.


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 TGFβ, and the influence of nicotinamide on TGFβ-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 TGFβ/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 TGFβ/SMADs signaling. This finding provides new therapeutic strategies and new ideas for clinical treatment.

SUBMITTER: Zhang C 

PROVIDER: S-EPMC11228357 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Therapeutic application of nicotinamide: As a potential target for inhibiting fibrotic scar formation following spinal cord injury.

Zhang Ce C   Shao Qiang Q   Zhang Ying Y   Liu Wenjing W   Kang Jianning J   Jin Zhengxin Z   Huang Nana N   Ning Bin B  

CNS neuroscience & therapeutics 20240701 7


<h4>Aim</h4>We aimed to confirm the inhibitory effect of nicotinamide on fibrotic scar formation following spinal cord injury in mice using functional metabolomics.<h4>Methods</h4>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 fun  ...[more]

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