Enhanced expression of osteopontin in human diabetic artery and analysis of its functional role in accelerated atherogenesis

We have previously reported that high glucose stimulates osteopontin (OPN) expression through protein kinase C-dependent pathways as well as hexosamin e pathways in cultured rat aortic smooth muscle cells. The finding prompted us to study in vivo expression of OPN in diabetes mellitus. In the present : study, we found by immunohistochemistry that medial layers of the carotid arteries of streptozotocin-induced diabetic rats and the forearm arteries of diabetic patients stained positively for OPN antibodies, whereas the sta ining from arteries of control rats and nondiabetic patients was negative. We also found that OPN stimulated the migration and enhanced platelet-deriv ed growth factor (PDGF)-mediated DNA synthesis of cultured rat aortic smoot h muscle cells. OPN and PDGF synergistically activated focal adhesion kinas e as well as extracellular signal-regulated kinase; this finding seems to e xplain the OPN-induced enhancement of PDGF-mediated DNA synthesis. Taken to gether, our present results raise a possibility that OPN plays a role in th e development of diabetic vascular complications.