The antimicrobial peptide APKGVQGPNG (named YD), a natural peptide originating from Bacillus amyloliquefaciens CBSYD1, exhibited excellent antibacterial and antioxidant properties in vitro. These characteristics are closely related to inflammatory responses which is the central trigger for liver fibrosis. However, the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied. In this study, we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of α-smooth muscle actin and collagen I in carbon tetrachloride-induced mice. Then we found that YD inhibited the level of miR-155, which plays an important role in inflammation and liver fibrosis. Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155. We demonstrate that YD significantly decreases the contents of inflammatory cytokines and suppresses the NF-κB signaling pathway. Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation, the downregulated levels of inflammatory cytokines, and the inactivation of the NF-κB pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155–Casp12–NF-κB axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.

抗菌肽APKGVQGPNG（命名为YD）是源自解淀粉芽孢杆菌CBSYD1的天然肽，在体外表现出出色的抗菌和抗氧化特性。这些特征与炎症反应密切相关，后者是肝纤维化的主要诱因。然而，很少研究YD对肝纤维化的治疗作用及其潜在机制。在这项研究中，我们显示YD可通过测量血清转氨酶活性和α的表达来改善肝功能并抑制肝纤维化的进展平滑肌肌动蛋白和胶原蛋白I在四氯化碳诱导的小鼠中。然后我们发现YD抑制了miR-155的水平，而miR-155在炎症和肝纤维化中起着重要作用。生物信息学分析和荧光素酶报告基因检测表明Casp12是miR-155的新靶标。我们表明，YD显著减少炎性细胞因子的内容，并抑制了NF- κ乙信号传导途径。进一步的研究表明在RAW264.7细胞中所述miR-155模拟物转染部分逆转的YD-介导CASP12上调，炎性细胞因子的下调的水平，和NF-的失活κ乙通路。总体而言，我们的研究表明YD通过miR- 155– Casp12减轻炎症-NF- κB轴在肝纤维化过程中提供了有希望的肝纤维化治疗候选药物。