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Relationship between the expression of advanced glycation end-products (AGE) and the receptor for AGE (RAGE) mRNA in
Daisuke Suzuki1, Masao Toyoda, Naoyuki Yamamoto
1Division of Nephrology and Metabolism, Department of Internal Medicine, School of Medicine, Tokai University, Isehara.
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.
Insights
Advanced glycation end-products (AGE) and the receptor for advanced glycation end-products (RAGE) are linked to kidney damage in diabetic nephropathy. Increased AGE and RAGE expression correlates with mesangial expansion in DN.
Area of Science:
- Nephrology
- Diabetology
- Molecular Biology
Background:
- The receptor for advanced glycation end-products (RAGE) is a cellular receptor for advanced glycation end-products (AGEs).
- Diabetic nephropathy (DN) is a serious complication of diabetes characterized by kidney damage.
- The roles of AGEs and RAGE in the pathogenesis of DN require further elucidation.
Purpose of the Study:
- To investigate the relationship between AGE protein and RAGE mRNA expression in renal tissues of patients with diabetic nephropathy (DN).
- To examine the correlation between AGE and RAGE expression and the degree of mesangial expansion in DN.
Main Methods:
- Renal biopsy tissues from 20 DN patients and 5 controls were analyzed.
- Immunohistochemistry for AGE protein and in situ hybridization for RAGE mRNA were performed.
- Glomerular mesangial expansion (%Mes) was quantified using an image analyzer.
Main Results:
- AGE protein was detected in the mesangial matrix of DN kidneys but not in controls.
- RAGE mRNA was expressed in glomerular cells in both DN and control samples.
- %Mes significantly correlated with both AGE protein staining intensity and RAGE mRNA expression.
Conclusions:
- Both AGEs and RAGE are associated with the development and progression of diabetic nephropathy.
- These findings highlight the potential involvement of the AGE-RAGE pathway in DN pathogenesis.
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