The antimicrobial peptide YD attenuates inflammation via miR-155 targeting CASP12 during liver fibrosis

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.KEY WORDS: Liver fibrosis, Inflammation, Antimicrobial peptide, MiR-155, CASP12