Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI.By generating myeloid-specific FoxO1-knockout mice, we observed that the deficiency of FoxO1 in myeloid cells protected against ischemia-reperfusion (I/R)-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Overall design: To investigate the funtion of FoxO1 in the regulation of macrophage during ischemia-reperfusion injury-induced acute kidney injury, we established ischemia-reperfusion injury model in mice with myeloid-specific FoxO1-knockout.