Wound healing and tissue regeneration are influenced by a variety of factors. Adverse lifestyle habits, such as excessive alcohol consumption, delay wound healing and increase the risk of secondary infections. Ethyl butyrate is a common food additive widely used to enhance the aroma of alcoholic beverages. This additive is generally considered harmless to human health in both industrial and domestic settings. However, the ecotoxicity and its effects on wound healing have not been elucidated. In this study, we used zebrafish as the experimental animal, and the caudal fins were amputated to explore the effects of ethyl butyrate on wound healing and tissue regeneration. The effect of ethyl butyrate on blastema and bone regeneration and its impact on the transcriptional levels of regeneration-related genes and inflammation-related genes were evaluated. RNA-seq was conducted to determine the differentially expressed genes (DEGs) between the treatment and the control groups. KEGG and GO analysis was conducted to explore the functions of DEGs. Significantly enriched GO terms and KEGG pathways were identified to explore the molecular mechanism underlying the inhibition of zebrafish caudal fin regeneration by ethyl butyrate. The results demonstrated that ethyl butyrate significantly inhibited the regeneration of zebrafish caudal fins, including blastema and bone regeneration. Ethyl butyrate exposure significantly downregulated the expression of genes associated with bone and blastema regeneration and inflammation response. KEGG and GO functional analyses revealed that the DEGs were associated with significant enrichment of extracellular matrix-receptor interactions. Ethyl butyrate treatment downregulated the expression of most extracellular matrix-related genes. These findings indicate that ethyl butyrate potentially modulates pathways associated with the structure, adhesion, modification, and degradation of the extracellular matrix, thereby disrupting extracellular matrix remodeling, inhibiting wound inflammation, impairing blastema and bone regeneration and ultimately hindering caudal fin regeneration. In summary, the findings demonstrate that ethyl butyrate disrupts extracellular matrix remodeling and inhibits the regeneration of zebrafish caudal fins. These results provide valuable insights into the rational use of ethyl butyrate and further investigation of wound healing mechanisms.

中文翻译：

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丁酸乙酯通过破坏细胞外基质重塑来抑制成年斑马鱼的尾鳍再生


伤口愈合和组织再生受多种因素的影响。不良的生活习惯，例如过量饮酒，会延迟伤口愈合并增加继发感染的风险。丁酸乙酯是一种常见的食品添加剂，广泛用于增强酒精饮料的香气。在工业和家庭环境中，这种添加剂通常被认为对人类健康无害。然而，生态毒性及其对伤口愈合的影响尚未阐明。在本研究中，我们以斑马鱼为实验动物，截去尾鳍，探讨丁酸乙酯对伤口愈合和组织再生的影响。评价丁酸乙酯对胚芽肿和骨再生的影响及其对再生相关基因和炎症相关基因转录水平的影响。进行 RNA-seq 以确定治疗组和对照组之间的差异表达基因 （DEGs）。进行 KEGG 和 GO 分析以探讨 DEGs 的功能。鉴定了显著富集的 GO 术语和 KEGG 通路，以探讨丁酸乙酯抑制斑马鱼尾鳍再生的分子机制。结果表明，丁酸乙酯显著抑制斑马鱼尾鳍再生，包括胚层和骨再生。丁酸乙酯暴露显着下调了与骨骼和胚层再生以及炎症反应相关的基因的表达。KEGG 和 GO 功能分析显示，DEGs 与细胞外基质-受体相互作用的显着富集有关。丁酸乙酯处理下调了大多数细胞外基质相关基因的表达。 这些发现表明，丁酸乙酯可能调节与细胞外基质的结构、粘附、修饰和降解相关的途径，从而破坏细胞外基质重塑，抑制伤口炎症，损害胚层和骨再生，并最终阻碍尾鳍再生。总之，研究结果表明丁酸乙酯破坏细胞外基质重塑并抑制斑马鱼尾鳍的再生。这些结果为合理使用丁酸乙酯和进一步研究伤口愈合机制提供了有价值的见解。