Activation of the polyol pathway depletes NADPH, leading to AGEs binding to their receptors on cell surfaces, resulting in oxidative stress, ROS generation, and activation of PKC and ERK1/2 signaling pathways, ultimately promoting TGF-β secretion, mesangial cell proliferation, and ECM synthesis, culminating in renal fibrosis [73]. Here, MAPK3 is linked to renal fibrosis.