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 close...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 liverfibrosis.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 a-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 signifi-cantly decreases the contents of inflammatory cytokines and suppresses the NF-k B 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-k B pathways.Collectively,our study indicates that YD reduces inflammation throughthe mi R-155 e Casp12 e NF-k B axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.展开更多
基金the National Natural Science Foundation of China(No.81602945,81673283,and 81874315)the CAMS Innovation Fund for Medical Sciences(CIFMS,No.2019-I2M-5-074,China)the Program for the Ministry of Education“Peptide Drugs”Innovation Team(No.IRT_15R27,China).
文摘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 liverfibrosis.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 a-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 signifi-cantly decreases the contents of inflammatory cytokines and suppresses the NF-k B 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-k B pathways.Collectively,our study indicates that YD reduces inflammation throughthe mi R-155 e Casp12 e NF-k B axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.
