Figure 3.

AGEs in diabetic kidney disease. Activation of the AGE–RAGE axis derived from the accumulation of AGEs in renal tissue induces tissue dysfunction through diverse mechanisms: (a) macrophage migration, which agglomerates in the renal glomerulus’s mesangium, establishing an inflammatory microenvironment led by IL-6 synthesis and, eventually, causing the expansion of this layer, compression of the capillary, and reduction of the body surface area of filtration. (b) Increased expression of transforming growth factor β (TGF-β), which stimulates fibrogenesis, collagen synthesis, and renal tubular cell apoptosis, leading to glomerular sclerosis. (c) Lipids storage from altered cholesterol metabolism as a result of the activation of sterol-regulatory element-binding protein 2 (SREBP-2), increasing the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) and, finally, concluding in increased cholesterol synthesis.