Objective  To investigate the effect of TRIM7, an E3 ubiquitin protein ligase, on lipid accumulation in foam cells derived from mouse bone marrow-derived macrophages (BMDMs) and its mechanism.

Methods  Western blot and qRT-PCR were used to detect the expression changes of TRIM7 in BMDMs stimulated by oxidized low-density lipoprotein. Construct TRIM7 knockout BMDMs and TRIM7 overexpression THP-1 cell lines, and analyze the effect of TRIM7 on lipid metabolism of BMDMs through qRT-PCR, oil red staining, and total cholesterol content detection. Western blot was used to detect the phosphorylation levels of MAPK signaling pathway proteins in BMDMs after TRIM7 knockout. Immunoprecipitation detection of the interaction between TRIM7 and the upstream kinase TAK1 in the MAPK pathway.

Results  TRIM7 interacted directly with TAK1, TRIM7 knockout could enhance the phosphorylation activity of MAPK signaling pathway protein, up regulate the expression of CD36 and MSR1 and inhibit the expression of ABCA1, increase cholesterol uptake and reduce lipid excretion, and ultimately promote the formation of foam cells.

Conclusion  TRIM7 negatively regulates lipid accumulation in foam cells by inhibiting MAPK signaling pathway and scavenger receptor expression by directly binding to TAK1, which provides a potential new target for the treatment of atherosclerosis.

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