Enhanced expression of osteopontin by high glucose in cultured rat aortic smooth muscle cells.
Enhanced expression of osteopontin by high glucose in cultured rat aortic smooth muscle cells.
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DOI：
10.1006/bbrc.1999.0701
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发表时间：
1999-05
影响因子：
3.1
通讯作者：
M. Takemoto;K. Yokote;M. Yamazaki;A. Ridall;W. Butler;T. Matsumoto;K. Tamura;Y. Saito;S. Mori
中科院分区：
文献类型：
--
作者：
M. Takemoto;K. Yokote;M. Yamazaki;A. Ridall;W. Butler;T. Matsumoto;K. Tamura;Y. Saito;S. Mori
动脉粥样硬化性血管疾病是糖尿病患者的主要并发症，骨桥蛋白最近被认为与动脉粥样硬化的发展有关。在本研究中，我们研究了高糖对培养的大鼠主动脉平滑肌细胞骨桥蛋白表达的影响。高浓度的葡萄糖增加了骨桥蛋白从细胞中的分泌，并完全抑制蛋白激酶C，GF 109203 X的抑制剂的分泌增加。北方印迹分析证实了葡萄糖对骨桥蛋白mRNA表达的增强作用。使用骨桥蛋白启动子/荧光素酶表达载体系统测量的骨桥蛋白的启动子活性被高糖增加，并且增强的作用被GF 109203 X完全抑制。氨基葡萄糖还增加了骨桥蛋白的启动子活性，而阿扎胞苷（谷氨酰胺：果糖-6-磷酸酰胺转移酶（氨基己糖途径的关键酶）的抑制剂）可显著抑制高葡萄糖介导的启动子活性增加。总之，这些数据表明，高葡萄糖可能通过激活蛋白激酶C以及己糖胺途径在转录水平上增强骨桥蛋白的表达。我们的研究结果表明，骨桥蛋白可能在糖尿病血管并发症的发展中发挥作用。
Atherosclerotic vascular disease is a major complication of diabetic patients, and osteopontin has recently been implicated in the development of atherosclerosis. In the present study, we have investigated the effects of high glucose on expression of osteopontin in cultured rat aortic smooth muscle cells. High concentrations of glucose increased osteopontin secretion from the cells, and the increased secretion was completely inhibited by an inhibitor of protein kinase C, GF109203X. Northern blot analysis confirmed the enhanced effect of glucose on expression of osteopontin mRNA. Promoter activity of osteopontin, measured using the osteopontin promoter/luciferase expression vector system, was increased by high glucose, and the enhanced effect was completely inhibited by GF109203X. Glucosamine also increased the promoter activity of osteopontin, and azaserine, an inhibitor of glutamine:fructose-6-phosphate amidotransferase (the key enzyme of the hexosamine pathway), profoundly inhibited high glucose-mediated increase in the promoter activity. Taken together, these data indicate that high glucose enhances the expression of osteopontin at the transcriptional level possibly through the activation of protein kinase C as well as the hexosamine pathway. Our results suggest that osteopontin could play a role in the development of diabetic vascular complications.