Enhanced expression of osteopontin by high glucose in cultured rat aortic smooth muscle cells

Atherosclerotic vascular disease is a major complication of diabetic patien ts, and osteopontin has recently been implicated in the development of athe rosclerosis. 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 inhib itor of protein kinase C, GF109203X Northern blot analysis confirmed the en hanced effect of glucose on expression of osteopontin mRNA. Promoter activi ty of osteopontin, measured using the osteopontin promoter/luciferase expre ssion vector system, was increased by high glucose, and the enhanced effect was completely inhibited by GF109203X. Glucosamine also increased the prom oter activity of osteopontin, and azaserine, an inhibitor of glutamine:ftuc tose-6-phosphate amidotransferase (the key enzyme of the hexosamine pathway ), profoundly inhibited high glucose-mediated increase in the promoter acti vity. Taken together, these data indicate that high glucose enhances the ex pression of osteopontin at the transcriptional level possibly through the a ctivation of protein kinase C as well as the hexosamine pathway. Our result s suggest that osteopontin could play a role in the development of diabetic vascular complications. (C) 1999 Academic Press.