Impact of S100A4 Deletion on the Macrophage Metabolome and Differentiation

Abstract Alterations in the macrophage metabolome greatly influence macrophage differentiation, subsequently impacting the development of diverse clinical diseases. Although S100A4 is a crucial factor in conditioned macrophage movement and inflammatory cell recruitment, its metabolism-mediated mechanism in regulating macrophage differentiation remains unclear. Here, we generated mice with a macrophage-specific S100A4 deletion by crossing C57BL/6J-S100a4 em1(flox)Cya mice with Lyz2-cre mice. Subsequently, macrophages were isolated from these mice, and heterozygous mouse macrophages served as controls for metabolomic analysis. The S100A4 deletion significantly influenced metabolic pathways, such as those involving lysophosphatidylserine, ceramide, and L-glutamate, which are implicated in modulating macrophage differentiation. This work elucidates the metabolic intricacies associated with the S100A4-mediated regulation of macrophage differentiation and provides a valuable reference for future investigations in this field.