AMADORI GLUCOSE ADDUCTS MODULATE MESANGIAL CELL-GROWTH AND COLLAGEN GENE-EXPRESSION
AMADORI GLUCOSE ADDUCTS MODULATE MESANGIAL CELL-GROWTH AND COLLAGEN GENE-EXPRESSION
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DOI：
10.1038/ki.1994.62
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发表时间：
1994-02-01
影响因子：
19.6
通讯作者：
ZIYADEH, FN
中科院分区：
文献类型：
--
作者：
COHEN, MP;ZIYADEH, FN
糖尿病血清中糖化蛋白浓度升高，优先转运到肾小球。我们研究了血清蛋白中Amadori葡萄糖加合物（体内循环糖化蛋白的主要形式）对肾小球系膜细胞的影响，肾小球系膜细胞是糖尿病肾病病变的起源。[H-3]-胸腺嘧啶与小鼠系膜细胞的结合明显受到抑制，当细胞在28 mM葡萄糖的糖化血清中培养4天，或者当细胞在糖化血清预包被的微滴板中培养时。单克隆抗体对糖化白蛋白中的Amadori加合物具有免疫反应，而对其他糖化血清蛋白或晚期糖化末端（AGE）产物无反应。糖化血清刺激IV型胶原基因表达，增加IV型胶原分泌，与糖化白蛋白中Amadori加合物反应的单克隆抗体也能阻止这一作用。糖基化诱导的细胞增殖、胶原合成和胶原基因表达的变化在葡萄糖浓度正常的培养基中观察到，在葡萄糖浓度高的培养基中被夸大。数据表明，糖化血清蛋白的Amadori产物诱导系膜细胞异常，这与糖尿病肾病的发病机制高度相关，当糖化血清蛋白出现在高血糖环境时，这些作用会加强。这些数据还表明系膜细胞特异性地识别糖化白蛋白中的Amadori加合物。
Diabetic serum contains increased concentrations of glycated proteins, which are preferentially transported into the renal glomerulus. We investigated effects of Amadori glucose adducts in serum proteins, the predominant form in which circulating glycated proteins exist in vivo, on glomerular mesangial cells, where the lesion of diabetic nephropathy originates. [H-3]-thymidine incorporation by murine mesangial cells was significantly inhibited when cells were grown in the presence of serum glycated by incubation for four days with 28 mM glucose or when cells were cultured in microtiter plates that had been precoated with glycated serum. This effect was prevented by a monoclonal antibody immunoreactive with Amadori adducts in glycated albumin, and unreactive with other glycated serum proteins or with advanced glycation end (AGE) products. Glycated serum stimulated Type IV collagen gene expression and increased Type IV collagen secretion, an effect also prevented by monoclonal antibodies reactive with Amadori adducts in glycated albumin. The glycation-induced changes in proliferation, collagen synthesis and collagen gene expression were observed in media containing normal glucose concentration and were exaggerated in media containing high glucose concentration. The data indicate that Amadori products of glycated serum proteins induce mesangial cell abnormalities that are highly relevant to the pathogenesis of diabetic nephropathy, and that these effects are accentuated when glycated serum proteins are presented in a hyperglycemic milieu. The data also suggest that mesangial cells specifically recognize Amadori adducts in glycated albumin.