Background The progression of diabetic kidney disease (DKD) is strongly associated with a chronic inflammatory microenvironment, with macrophage polarization imbalance recognized as a pivotal driver. Maresin 1 (MaR1), a specialized proresolving lipid mediator, plays a crucial role in restoring immune homeostasis across various inflammatory conditions. However, its precise role in ameliorating kidney injury through macrophage polarization in DKD remains unclear. Methods The type 2 diabetes mouse model was established using a high‐fat diet combined with streptozotocin induction. The therapeutic efficacy of MaR1 was assessed by evaluating metabolic parameters (blood glucose, lipid profile), renal function (urine albumin‐to‐creatinine ratio ACR, serum creatinine, and blood urea nitrogen BUN), and renal pathology (HE staining and Masson staining). In vitro, bone marrow‐derived macrophages (BMDMs) were exposed to high glucose, and the modulatory effect of MaR1 on M1/M2 polarization was assessed using RT‐qPCR, immunohistochemistry, and immunofluorescence. Results MaR1 treatment significantly ameliorated metabolic abnormalities in diabetic mice (lower blood glucose and cholesterol), improved renal function (reduced ACR, serum creatinine, and BUN), and attenuated renal fibrosis (all p < 0.05). Mechanistically, MaR1 reversed macrophage polarization imbalance both in vivo and in vitro, promoting a shift from the M1 phenotype (downregulation of iNOS and TNF‐α) to the M2 phenotype (upregulation of Arg‐1 and IL‐10). Conclusion MaR1 improves metabolic disturbances and renal injury in DKD by driving macrophage polarization toward the M2 phenotype and restoring immune homeostasis. These findings highlight MaR1 as a promising candidate for targeted immunomodulatory therapies in DKD.
Pu et al. (2026) studied this question.