Fig. 2

Potential signaling pathways involved in diabetic nephropathy (DN) pathogenesis. Activation of receptor of advanced glycation end-products (RAGE) by advanced glycation end-products (AGEs) results in reactive oxidative species (ROS) overproduction, leading to oxidative stress. Meanwhile, the polyol pathway activated by intracellular glucose further aggravates the oxidative stress. Activation of protein kinase C (PKC) via the polyol pathway is another major source of ROS production. Mitochondrial damage also contributes to ROS production. ROS overproduction and impaired anti-oxidant response cause oxidative stress, which activates nuclear factor (NF)-κB and upregulates monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β. Thereafter, the inflammation induces endoplasmic reticulum (ER) stress via unfolded protein response pathways, resulting in metabolic disorders and apoptosis