The involvement of proinflammatory cytokines indiabetic nephropathy: Focus on interleukin 1 (Il-1), interleukin 6 (Il-6), and tumor necrosis factor-alpha (TNF-Α) signaling mechanism

About 20-40% of type 2 diabetic patients may develop diabetic nephropathy (DN) as its complication. The pathogenesis of DN is complex. Classically, metabolic and hemodynamic impairment are considered as its pathogenesis. However, large number of evidences point that inflammation is a key event in the development and progression of DN. Among several inflammatory molecules, pro-inflammatory cytokines such as interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) are known to be involved. Chronic condition of hyperglycemia responsible for the formation of pro-inflammatory cytokines via advanced glycation end products (AGE) pathway and protein kinase C (PKC) pathway. These pro-inflammatory cytokines exert signaling pathway that lead to extracellular matrix (ECM) accumulation, glomerular basement membrant (GBM) thickening, and glomerulosclerosis, ultimately lead to development and progression of diabetic nephropathy. Understanding the detail of this mechanism will be beneficial for future research or treatment development of DN. Intervention in these signaling pathways may lead to development of novel therapeutic approach.