Randomized trial investigates let-7b's role in macrophage survival in inflammatory conditions, indicating potential therapy for atherosclerosis.
Key Points
This study aims to clarify the regulatory mechanisms of let-7b in macrophage polarization and survival.
Bone marrow-derived macrophages (BMDMs) from wild-type and let-7b knockout mice were polarized with cytokines.
Functional assessments including apoptosis, mitochondrial activity, and lipid droplet formation were conducted.
Proteomic profiling and immunoprecipitation of AGO2 complexes were performed alongside prime-RNA sequencing for target enrichment analysis.
Let-7b knockout increased iron content and ROS levels in anti-inflammatory macrophages while enhancing mitochondrial activity in pro-inflammatory macrophages.
Deficiency of let-7b reduced apoptosis and promoted proliferation in IL-4 stimulated BMDMs.
Upregulation of afadin (Afdn) was linked to increased cell survival in anti-inflammatory macrophages, demonstrating its non-canonical targeting by let-7b.