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.


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.
Suzuki
Daisuke
D
Division of Nephrology and Metabolism, Department of Internal Medicine, School of Medicine, Tokai University, Isehara.
Toyoda
Masao
M
Yamamoto
Naoyuki
N
Miyauchi
Masaaki
M
Katoh
Mayuko
M
Kimura
Moritsugu
M
Maruyama
Mayumi
M
Honma
Masashi
M
Umezono
Tomoya
T
Yagame
Mitsunori
M