Relationship between the Expression of Advanced Glycation End-Products (AGE) and the Receptor for AGE (RAGE) mRNA in Diabetic Nephropathy

Objective: The receptor for advanced glycation end-products (RAGE) is one of several advanced glycation end-product (AGE)-specific cellular receptors. To evaluate the relationship between AGE and RAGE in renal tissues of diabetic nephropathy (DN), we examined the levels of expression of AGE protein and of RAGE mRNA. We also investigated the relationships among the degree of mesangial expansion and the expression of AGE and RAGE mRNA. Patients and Methods: Renal biopsy tissues were obtained from 20 patients with DN. We performed immunohistochemical staining using monoclonal anti-AGE antibody and in situ hybridization using non-radioactive oligonucleotide RAGE probe on these tissues. We also examined five control renal samples. We evaluated the intensity of positive anti-AGE antibody staining and the percentage of cells positive for RAGE mRNA. We also measured the total glomerular area and mesangial area in glomeruli using an automatic image analyzer. We then calculated the percentage of mesangial area as a proportion of the total glomerular area (%Mes). Results: Anti-AGE antibody was detected in the expanded mesangial matrix in DN but not in control samples. RAGE mRNA expression was detected mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells, in both DN and control. %Mes correlated significantly with both the intensity of anti-AGE antibody positive staining and the percentage of cells positive for RAGE mRNA. Conclusions: Our findings suggest that both AGE and RAGE are associated with the development and progression of DN.