Maresin 1 Ameliorates Diabetic Kidney Disease in Mice by Promoting Macrophage M2 Polarization

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.