ADVANCED GLYCOSYLATION END PRODUCTS AND EFFECT OF MESANGIAL CELLS

终末期肾小球硬化是糖尿病的主要并发症 糖尿病。I型和II型肾小球病变 糖尿病相似表明葡萄糖代谢异常可能 参与他们的发展。高血糖导致 晚期糖基化终末产物的积累。这些产品 参与异常的、非代谢的胞外交联物 矩阵组件。它们的积累可能会导致硬化症 在糖尿病患者中观察到。年龄引发了大量的生物性 由表面受体介导的反应 巨噬细胞、内皮细胞、人和大鼠的特征 系膜细胞。 不同糖基化细胞外基质上的系膜细胞 这些成分会产生更多的纤维连接蛋白。使用普通鼠标 ，我们研究了年龄对系膜细胞合成的影响。 基底膜成分。培养的细胞在AGE上显示出水平的增加 使用核糖核酸酶保护分析的下列mRNAs：IV型胶原， 蛋白多糖、硫酸乙酰肝素、层粘连蛋白A和B链。我们还发现 IV型胶原蛋白释放到介质中的增加。这一速度 转录，通过核流失分析测量，也被刺激在 细胞接种在糖化牛血清白蛋白上。AGE受体抗体 抑制观察到的mRNAs的增加。抗血小板衍生生长因子的抗体使 年龄反应。这些观察提供了进一步的证据表明 糖尿病患者细胞外基质成分的蓄积受到调节 在基因水平上，并与系膜细胞的增加相关 营业额。

End-stage glomerulosclerosis constitutes a major complication of diabetes mellitus. The fact that the glomerular lesions of both type I and type II diabetes are similar suggests that abnormalities in glucose metabolism may participate in their development. Hyper-glycemia leads to the accumulation of advanced glycosylation end-products. These products participate in abnormal, non-metabolizable cross-linking of extra-cellular matrix components. Their accumulation may contribute to the sclerosis observed in diabetics. AGEs trigger a large number of biological reactions which are mediated by surface receptors that have been characterized on macrophages, endothelial cells, and human and rat mesangial cells. Mesangial cells plated on various glycosylated extracellular matrix components produce an increased amount of fibronectin. Using normal mouse mesangial cells, we investigated the effect of AGE on the synthesis of the basement membrane components. Cells plated on AGE showed increased levels of the following mRNAs using the RNAse protection assay: collagen type IV, proteoglycan heparan sulfate, and laminin A and B chains. We also found an increased release of collagen type IV into the medium. The rate of transcription, measured by nuclear run-off assays, was also stimulated in cells plated on glycosylated bovine serum albumin. AGE receptor antibodies inhibited the observed increase in mRNAs. Antibodies to PDGF abrogated the AGE response. These observations provide further evidence that the accumulation of extracellular matrix components in diabetics is regulated at the gene level, and is correlated with an increase in mesangial cell turnover.