Therapeutic application of nicotinamide: As a potential target for inhibiting fibrotic scar formation following spinal cord injury
》》Journal：CNS Neurosci Ther .
》》相关产品：SIS3 (SJ-MX0365)
》》产品引用描述：
》》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.
》》部分实验数据展示：
FIGURE 9: NAM mediated the inhibition of TGF-β/SMADs pathway in vitro. MEFs were overnight preconditioned with NAM (5 mM) or SIS3 (3 μM), then cultured and incubated with TGFβ (10 ng/mL) for 0, 15, 30, 60 min, or 24 h. (A, B) WB results showing the expression of phospho-SMAD2, phospho-SMAD3, SMAD2, and SMAD2/3 proteins in vitro. (C, D) WB analysis of phosphorylated ERK1/2 and ERK1/2 protein expression in vitro. (E, F) Nuclear translocation of SMAD2/3 in primary MEFs was determined by IF (scale bar = 25 μm) and quantitative analysis was performed by ImageJ. (G, H) Expression of SMAD4 and SMAD7 proteins was determined by WB. (I) The expression of Col1α1, Col4α1, Fn1, Actα2, Col1α2, and Vimentin in vitro was detected by RT-qPCR.
