ISG15 Promotes Cholesterol Efflux In THP-1 Macrophage Through MiR-17-5p/beclin-1 Pathway

Objective: ISG15(Interferon Stimulating Gene 15)is a small molecule protein encoded by the interferon-stimulating gene.ISG15 has a wide range of physiological effects,involved in inflammation,apoptosis and autophagy and other biological processes.And studies have shown that ISG15 has the role of anti-heart failure,suggesting that ISG15 is also closely related with cardiovascular disease.Atherosclerosis is one of the leading causes of death as a risk factor for cardiovascular disease.However,the studys about ISG15 on the occurrence and development of atherosclerosis are not clarified.In this study,we selected THP-1macrophage-derived foam cells as the research object,and explored the potential mechanism of ISG15 on macrophage cholesterol efflux from the cell level.Methods: THP-1 macrophage-derived foam cells were incubated with ISG15.The expression of ABCA1 and autophagy-related protein mRNA in THP-1 macrophage-derived foam cells were detected by fluorescence quantitative PCR.The expression of ABCA1 protein andautophagy-related protein was detected by Western blot.The miRNAs with potential binding sites of Beclin-1 were predicted and analyzed for their free energy and associated species conservation analysis.Cells were treated with interfering RNA and autophagic inhibitors to determine the effect of cell cholesterol efflux.Results: ISG15 can increase the ability of cholesterol efflux in THP-1 macrophage-derived foam cells.MiR-17-5p can target Beclin-1and inhibit the expression of Beclin-1.ISG15 inhibits the negative effect of miR-17-5p on Beclin-1,and increases the expression of Beclin-1.ISG15 enhances Beclin-1-mediated autophagy.Conclusions: ISG15 inhibits the negative regulation of miR-17-5p on Beclin-1 by reducing miR-17-5p,increases the expression of Beclin-1,and ultimately activates autophagy to increase cholesterol efflux.