Suzuki Daisuke, Toyoda Masao, Yamamoto Naoyuki, Miyauchi Masaaki, Katoh Mayuko, Kimura Moritsugu, Maruyama Mayumi, Honma Masashi, Umezono Tomoya, Yagame Mitsunori
Division of Nephrology and Metabolism, Department of Internal Medicine, School of Medicine, Tokai University, Isehara.
Intern Med. 2006;45(7):435-41. doi: 10.2169/internalmedicine.45.1557. Epub 2006 May 1.
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.
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).
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.
Our findings suggest that both AGE and RAGE are associated with the development and progression of DN.
晚期糖基化终末产物受体（RAGE）是几种晚期糖基化终末产物（AGE）特异性细胞受体之一。为了评估糖尿病肾病（DN）肾组织中AGE与RAGE之间的关系，我们检测了AGE蛋白和RAGE mRNA的表达水平。我们还研究了系膜扩张程度与AGE和RAGE mRNA表达之间的关系。
从20例DN患者获取肾活检组织。我们对这些组织使用单克隆抗AGE抗体进行免疫组织化学染色，并使用非放射性寡核苷酸RAGE探针进行原位杂交。我们还检测了5个对照肾样本。我们评估了抗AGE抗体染色阳性强度以及RAGE mRNA阳性细胞百分比。我们还使用自动图像分析仪测量肾小球中的总肾小球面积和系膜面积。然后我们计算系膜面积占总肾小球面积的百分比（%Mes）。
在DN患者扩张的系膜基质中检测到抗AGE抗体，而在对照样本中未检测到。在DN和对照样本中，RAGE mRNA表达主要在肾小球固有细胞中检测到，包括肾小球系膜细胞和上皮细胞。%Mes与抗AGE抗体阳性染色强度和RAGE mRNA阳性细胞百分比均显著相关。
我们的研究结果表明，AGE和RAGE均与DN的发生和发展有关。
