Diabetic vasculopathy is a multifactor disease. AGE-RAGE interactions are thought to play a central role in the development of diabetic vascular complications.When made as a diabetic model,RAGE-overexpressing transgenic mice exhibited the exacerbation of the indices of nephropathy, and this was prevented by the inhibition of AGE formation. Extracellular signals and nuclear factors that induce the transcription of human RAGE gene were identified, which could be regard as risk factors of diabetic complications. Through an analysis of polysomal mRNAs for RAGE, three major variants were isolated:novel C-terminally and N-terminally truncated forms and the known full-length form. The former, soluble form of RAGE,named endogenous secretory RAGE(esRAGE), was able to capture AGE ligands and neutralize the AGE action on endothelial cells, suggesting that this variant has a potential to protect blood vessels from diabetes-induced injury. |