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。高血糖导致蓄积 晚期糖基化终末产物参与异常、非 细胞外基质成分的可代谢交联性。他们的 蓄积可能是糖尿病患者出现硬化症的原因之一，因为 AGEs通过表面引发大量的生物反应 巨噬细胞、内皮细胞、 人和大鼠肾小球系膜细胞。系膜细胞在不同材料上的电镀 糖基化细胞外基质的成分会产生过量的 纤维连接蛋白。利用正常的小鼠系膜细胞，我们研究了 年龄对基底膜成分合成的影响。单元格 AGE组IV型胶原基因表达水平升高， 使用核糖核酸酶的蛋白多糖、硫酸肝素和层粘连蛋白A和B链 保护性化验。IV型胶原的释放也增加了。 在媒介中。转录速度，通过核径流来测量 在糖化牛血清培养的细胞中也能被刺激。 白蛋白。这些观察提供了进一步的证据，证明 糖尿病患者细胞外基质成分的表达受基因调控 水平。

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 which participate in abnormal, non- metabolizable cross-linking of extra-cellular matrix components. Their accumulation may contribute to the sclerosis observed in diabetics, since AGEs trigger a large number of biological reactions through surface receptors that have been characterized on macrophages, endothelial cells, and human and rat mesangial cells. Mesangial cells plated on various components of glycosylated extracellular matrix produce an excess 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 mRNA levels of collagen type IV, proteoglycan heparan sulfate, and laminin A and B chains using the RNase protection assay. There was also an increased release of collagen type IV in the medium. The rate of transcription, measured by nuclear run-off assays, was also stimulated in cells plated on glycosylated bovine serum albumin. These observations provide further evidence that the accumulation of extra-cellular matrix components in diabetics is regulated at the gene level.