Y- box binding protein 1 regulates ox-LDL mediated inflammatory responses and lipid uptake in macrophages

Abstract Aims Y-box protein 1 (YB1) is a key regulator of inflammatory mediators. However, the roles of YB1 in oxidized low-density lipoprotein (ox-LDL)-induced macrophage inflammation and lipid uptake remain less understood. Thus, we explored the roles of YB1 in ox-LDL-induced macrophage inflammation and lipid uptake and its underlying molecular mechanisms. Methods An ox-LDL-induced atherosclerosis (AS) model was used in this study. Western blotting, RT-PCR, immunofluorescence, ELISA, dil-ox-LDL staining, a dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) and in vivo experiments were used to detect each target. Results ox-LDL downregulates YB1 expression in THP-1-derived macrophages and human monocyte-derived macrophages (hMDMs) via the NF-κB pathway. Downregulation of YB1 is facilitated by lipid uptake in macrophages, and CD36 is involved in this process. Furthermore, YB1 suppresses CD36 protein levels by directly binding to the coding sequence of the CD36 gene to promote CD36 mRNA decay but does not affect its mRNA transcription. Additionally, YB1 knockdown enhances the inflammatory response and lipid deposition via the NF-κB pathway in vivo. Conclusion ox-LDL decreases YB1 expression in macrophages, resulting in enhanced inflammatory responses by affecting NF-κB and facilitating lipid uptake by promoting scavenger receptor CD36 mRNA decay.