Emerging role of macrophages in diabetic nephropathy

Abstract Increasing evidence shows that diabetic nephropathy is associated with immune disorder. Macrophages are a key immune cell infiltrating the kidney in both patients and experimental animal models of diabetes, and correlate with progressive renal injury under diabetic conditions. Blockade of renal macrophage infiltration by either genetic deletion or pharmacological inhibition has been shown to improve diabetic renal injury, revealing a pathogenic role of macrophages in diabetic nephropathy. Further, studies identify that M1 macrophages are a key player responsible for diabetic renal injury by triggering renal inflammation, while M2 macrophages are highly heterogenous, and may play diverse roles in either initiating the renal repairing process if renal inflammation is resolved, or promoting progressive renal fibrosis via a macrophage-to-myofibroblast transition (MMT) process if renal inflammation is ongoing. Macrophages may also interact with intrinsic kidney cells to mediate renal inflammation or fibrosis directly or indirectly by producing a variety of proinflammatory cytokines/chemokines and growth factors, or by macrophage-derived exosomes. In summary, macrophages are immunologically important in the pathogenesis of diabetic kidney disease and may play a driving role in the progression of diabetic nephropathy. Targeting macrophages may thus be considered as a novel therapy for combatting diabetic nephropathy.