ADVANCED GLYCATION END-PRODUCTS UP-REGULATE GENE-EXPRESSION FOUND IN DIABETIC GLOMERULAR-DISEASE
ADVANCED GLYCATION END-PRODUCTS UP-REGULATE GENE-EXPRESSION FOUND IN DIABETIC GLOMERULAR-DISEASE
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DOI：
10.1073/pnas.91.20.9436
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发表时间：
1994-09-27
影响因子：
11.1
通讯作者：
STRIKER, LJ
中科院分区：
文献类型：
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作者：
YANG, CW;VLASSARA, H;STRIKER, LJ
一些证据表明，细胞外基质在糖尿病肾脏肾小球中的过度积累可能是由于葡萄糖和基质蛋白之间形成的活性中间体，称为晚期糖基化终产物（AGEs）。正常小鼠腹腔注射AGE修饰的小鼠血清白蛋白4周，检测肾小球细胞外基质、生长因子mRNA水平和形态学。我们发现AGE诱导肾小球细胞外基质α 1（IV）胶原、层粘连蛋白B1和转化生长因子β（1）mRNA水平增加（通过竞争性PCR测量），以及肾小球肥大。AGE反应是特异性的，因为同时给予AGE抑制剂氨基胍，减少了所有这些变化。我们的结论是，AGEs影响的基因表达，在糖尿病肾病，并可能发挥重要作用。
Several lines of evidence suggest that the excessive accumulation of extracellular matrix in the glomeruli of diabetic kidneys may be due to reactive intermediates forming between glucose and matrix proteins called advanced glycation end products (AGEs). Normal mice received AGE-modified mouse serum albumin i.p. for 4 weeks, and glomerular extracellular matrix, growth factor mRNA levels, and morphology were examined. We found that AGE induced an increase in glomerular extracellular matrix alpha 1(IV) collagen, laminin B1, and transforming growth factor beta(1) mRNA levels, as measured by competitive PCR, as well as glomerular hypertrophy. The AGE response was specific because the coadministration of an AGE inhibitor, aminoguanidine, reduced all these changes. We conclude that AGEs affected expression of genes implicated in diabetic kidney disease and may play a major role in nephropathy.