The polarization of macrophages participates in the repair after folic acid-induced acute kidney injury

Acute kidney injury (AKI) remains a major public health challenge, posing serious threats to human health. Increasing evidence indicates that renal cells undergo significant metabolic alterations following AKI, with inflammatory responses persisting throughout both injury and repair phases. Our previous research has demonstrated that heightened aerobic glycolysis after AKI leads to increased secretion of metabolic byproducts such as lactate, which plays a critical role in tissue repair. However, the relationship between metabolic reprogramming and inflammatory responses, as well as the underlying mechanisms, remain poorly understood. This study aims to clarify the regulatory effects of the glycolytic byproduct lactate on macrophage activation and phenotypic differentiation following AKI. We observed increased expression of M1/M2 macrophages and elevated secretion of inflammatory cytokines after folic acid-induced AKI. Immunofluorescence staining showed co-localization of macrophages with α-SMA. Manipulating lactate levels post-injury led to a decrease in macrophage expression and a reduction in fibroblast activation and proliferation, ultimately impairing renal tissue repair. These findings suggest that targeting lactate as a key regulator of macrophage phenotype differentiation may provide a theoretical and clinical foundation for therapeutic strategies in AKI repair.

AKI; Glycolysis; Lactate; Macrophage; Phenotype.