Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis of the skin and internal organs. Despite several studies on SSc treatments, effective treatments for SSc are still lacking. Since evidence suggests an association between intestinal microbiota and SSc, we focused on butyrate, which has beneficial effects in autoimmune diseases as a bacterial metabolite. Here, we investigated the therapeutic potential of sodium butyrate (SB) using a bleomycin-induced fibrosis mouse model of SSc and human dermal fibroblasts (HDFs). SB attenuated bleomycin-induced dermal and lung fibrosis in mice. SB influenced fecal microbiota composition (phyla Actinobacteria and Bacteroidetes, genera Bifidobacterium and Ruminococcus_g2). SB controlled macrophage differentiation in mesenteric lymph nodes, spleen, and bronchoalveolar lavage cells of mice with bleomycin-induced skin fibrosis. Profibrotic and proinflammatory gene expression was suppressed by SB administration in skin. Furthermore, SB inhibited transforming growth factor β1-responsive proinflammatory expression with increased acetylation of histone 3 in HDFs. Subcutaneous SB application had antifibrogenic effects on the skin. Butyrate ameliorated skin and lung fibrosis by improving anti-inflammatory activity in a mouse model of SSc. Butyrate may exhibit indirect and direct anti-fibrogenic action on fibroblasts by regulating macrophage differentiation and inhibition of histone deacetylase 3. These findings suggest butyrate as an SSc treatment.
Background As an instrument for measuring body composition in experimental animals, dual energy X-ray absorptiometry (DXA) is ideal for accuracy, cost, and measurement efficiency. However, there is too little insight into the effectiveness of the various aspects of applying DXA to experimental animals. We investigated whether to compare and verify the precision and accuracy of DXA and nuclear magnetic resonance (NMR) animal body composition analyzers. Methods We used 30 Institution of Cancer Research mice in the study. First, in order to evaluate the reproducibility of DXA and NMR, we did repeated measurements by repositioning each mouse in anesthesia and euthanasia states. Subsequently, the accuracy of each device was evaluated by comparing the weight measured before the experiment, the weight of the tissue extracted from the mice after the experiment, and the measured DXA and NMR. In addition, when measuring the body composition of animals, we compared the time and the measurable body composition parameters and summarized the advantages and disadvantages of the 2 devices. Results Compared to NMR, DXA had the advantage of a fast measurement of bone composition and rapid image analysis. In addition, DXA showed a higher correlation (>95%) with fat mass, lean mass baseline than did NMR (>85%). Conclusions In conclusion, DXA was confirmed to have higher precision and measurement accuracy than did NMR. Therefore, DXA is an effective method for evaluating the body composition of experimental animals.
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