Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy

Many lines of evidence, ranging from in vitro experiments and pathological examinations to epidemiological studies, show that inflammation is a cardinal pathogenetic mechanism in diabetic nephropathy. Thus, modulation of inflammatory processes in the setting of diabetes mellitus is a matter of great interest for researchers today. The relationships between inflammation and the development and progression of diabetic nephropathy involve complex molecular networks and processes. This Review, therefore, focuses on key proinflammatory molecules and pathways implicated in the development and progression of diabetic nephropathy: the chemokines CCL2, CX3CL1 and CCL5 (also known as MCP-1, fractalkine and RANTES, respectively); the adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion protein 1, endothelial cell-selective adhesion molecule, E-selectin and a-actinin 4; the transcription factor nuclear factor kappa B; and the inflammatory cytokines IL-1, IL-6, IL-18 and tumor necrosis factor. Advances in the understanding of the roles that these inflammatory pathways have in the context of diabetic nephropathy will facilitate the discovery of new therapeutic targets. In the next few years, promising new therapeutic strategies based on anti-inflammatory effects could be successfully translated into clinical treatments for diabetic complications, including diabetic nephropathy.