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

Abstract

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- κ 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- κ B pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155– Casp12 –NF- κ B axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.

Phillygenin Attenuates Carbon Tetrachloride-Induced Liver Fibrosis via Modulating Inflammation and Gut Microbiota

“…Correspondingly, we investigated the expressions of α-SMA and Collagen I. Immunostaining showed that the α-SMA and Collagen I expressions were significantly higher in the CCl 4 group than the solvent control group. Our results were in agreement with the findings of Yan et al ( Yan et al, 2021 ). This indicates that CCl 4 is able to promote the activation of HSCs as well as the accumulation of ECM.…”

Antimicrobial peptides: mechanism of action, activity and clinical potential

“…Experimental studies revealed that LL-37 [ 299 ] and S100 peptide [ 300 ] in keloid tissues mitigated collagen production, supporting the AMPs’ antifibrogenic properties. Yan et al [ 301 ] recently reported that the anti-fibrotic properties of AMP YD were mediated through the miR-155/Casp12/NF-kB pathway. In addition, the recombinant LL-37 can induce endothelial cell proliferation, migration and formation of tubule-like structures, and increase vascularization and re-epithelialization in mouse trauma experiments [ 302 ].…”

The Upregulation of Leucine-Rich Repeat Containing 1 Expression Activates Hepatic Stellate Cells and Promotes Liver Fibrosis by Stabilizing Phosphorylated Smad2/3

“…Liver fibrosis serves as a crucial pathological stage in the progression of liver cancer. Despite the promising outcomes observed in preclinical investigations, the effectiveness of antifibrotic candidates in clinical trials is limited [ 5 , 6 , 7 , 34 ]. Thus, more potential targets for the development of anti-liver-fibrosis therapeutics with thoroughly explained molecular mechanisms are urgently needed.…”

“…If uncontrolled, liver fibrosis gradually progresses to liver cirrhosis and even hepatocellular carcinoma (HCC), ultimately leading to organ dysfunction and mortality and seriously threatening human health [ 2 , 3 , 4 ]. Unfortunately, there is still a lack of effective medical therapies for the treatment of liver fibrosis [ 5 , 6 , 7 ]. Thus, an in-depth understanding of the molecular basis of liver fibrosis is important and necessary for supporting the development of novel antifibrotic therapies.…”