Hyperglycemia-induced alteration of vascular smooth muscle phenotype.
We have previously reported that high glucose stimulates osteopontin (OPN) expression through protein kinase C-dependent pathway, as well as the hexosamine pathway, in cultured rat aortic smooth muscle cells (SMC). 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 (STZ)-induced diabetic rats, as well as the forearm arteries of diabetic patients, stained positive with OPN antibodies, whereas the staining of control rats, as well as nondiabetic patients, was negative. We also found that OPN stimulated migration and enhanced platelet-derived growth factor (PDGF)-mediated DNA synthesis of cultured rat aortic SMC. OPN and PDGF synergistically activated focal adhesion kinase (FAK), as well as extracellular signal-regulated kinase (ERK), which seems to be a reason for OPN-induced enhancement of PDGF-mediated DNA synthesis. Taken together, our present results raise a possibility that OPN plays a role in the development of diabetic vascular complications.
Mori
Seijiro
S
Second Department of Internal Medicine, School of Medicine, Chiba University, 1-8-1 Inohana, 260-0856, Chiba, Japan.
Takemoto
Minoru
M
Yokote
Koutaro
K
Asaumi
Sunao
S
Saito
Yasushi
Y
D000818:Animals; D001011:Aorta; D000077214:Becaplermin; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006943:Hyperglycemia / Q000503:physiopathology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D053495:Osteopontin; D010750:Phosphoproteins / Q000494:pharmacology / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D012795:Sialoglycoproteins / Q000494:pharmacology / Q000502:physiology
D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D000077214:Becaplermin; D020928:Mitogen-Activated Protein Kinases