OVEREXPRESSION OF FIBRONECTIN INDUCED BY DIABETES OR HIGH GLUCOSE - PHENOMENON WITH A MEMORY
OVEREXPRESSION OF FIBRONECTIN INDUCED BY DIABETES OR HIGH GLUCOSE - PHENOMENON WITH A MEMORY
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DOI：
10.1073/pnas.87.1.404
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发表时间：
1990-01-01
影响因子：
11.1
通讯作者：
LORENZI, M
中科院分区：
文献类型：
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作者：
ROY, S;SALA, R;LORENZI, M
为了确定可能导致糖尿病并发症可逆性差的事件和机制，我们研究了糖尿病或高葡萄糖是否诱导基因表达的变化，以及这种变化是否持续代谢异常的存在。这项研究集中在纤连蛋白上，因为在糖尿病组织中发现的这种糖蛋白的数量增加，并且增厚的基底膜尚未得到解释。在链脲佐菌素诱导的糖尿病大鼠中，纤连蛋白mRNA水平增加至304 ± 0.05。对照组的295%（平均值± 0.5%）SD）（P <0.02），而271. ±.心肌肌动蛋白mRNA表达水平为对照组的27.3%（P <0.02）。纤连蛋白mRNA的升高持续数周后恢复接近正常。在培养的人内皮细胞中，高糖诱导的纤连蛋白和IV型胶原蛋白的过度表达在没有高糖的情况下重新铺板和多次细胞分裂后仍然可以检测到。长期暴露于高葡萄糖后转移到正常葡萄糖培养基的细胞也表现出比长期维持在正常葡萄糖中的细胞增殖优势。因此，糖尿病增加了作为并发症的已知靶点的组织中的纤连蛋白表达，并且该作用不容易逆转。体外研究表明，高血糖症可能通过诱导基因表达的自我持续变化而导致这些事件。
To identify events and mechanisms that might contribute to the poor reversibility of diabetic complications, we examined whether diabetes or high glucose induces change in gene expression and whether such changes outlast the presence of the metabolic abnormalities. The study focused on fibronectin because of increased amounts of this glycoprotein found in diabetic tissues and thickened basement membranes are as yet unexplained. In streptozotocin-induced diabetic rats, fibronectin mRNA levels were increased to 304 .+-. 295% of control (mean .+-. SD) in the kidney cortex (P < 0.02), and to 271 .+-. 273% of control in the heart (P < 0.02), while actin mRNA levels remained unchanged. Elevation of fibronectin mRNA persisted for weeks after restoration of near-normoglycemia. In cultured human endothelial cells, high glucose-induced overexpression of fibronectin and collagen IV remained detectable after replating and multiple cell divisions in the absence of high glucose. Cells shifted to normal-glucose medium after prolonged exposure to high glucose also exhibited a proliferative advantage over cells chronically maintained in normal glucose. Thus, diabetes increases fibronectin expression in tissues that are known targets of the complications, and the effect is not readily reversible. The in vitro studies suggest that hyperglycemia may be responsible for these events through induction of self-perpetuating changes in gene expression.