Latent transforming growth factor-beta binding protein-1, a component of latent transforming growth factor-beta complex, accelerates the migration of aortic smooth muscle cells in diabetic rats through integrin-beta3.
Aortic smooth muscle cells (SMCs) of diabetic animals have unique properties, including the overexpression of transforming growth factor-beta (TGF-beta) type II receptor, fibronectin, and platelet-derived growth factor beta-receptor. TGF-beta1 is produced and secreted as latent high-molecular weight complex consisting of mature TGF-beta1, latency-associated peptide (LAP), and a latent TGF-beta1 binding protein (LTBP-1). LAP has an important function in the latency of TGF-beta complex, but the role of LTBP-1 is not known in diabetic angiopathy. SMC migration from the medial layer to the intimal layer of an artery is an initial major process of the formation of intimal thickening of an artery. Migration activities of SMCs from diabetic rat with 1-500 pg/ml of LTBP-1 increased significantly compared with that without LTBP-1. LTBP-1 at 10-500 pg/ml stimulated the migration of diabetic SMCs more than SMCs from control rat. An anti-integrin-beta(3) antibody reduced LTBP-1-stimulated migration of diabetic SMCs to 51% compared with no antibody, but it did not reduce that of control SMCs. Furthermore, cross-linking experiments show that LTBP-1 binds integrin-beta(3) in diabetic SMCs much more than in control SMCs in coincidence with the increase of integrin-beta(3) in diabetic aorta by immunohistochemistry. Taken together, these observations suggest that LTBP-1 plays a critical role in intimal thickening of diabetic artery through the acceleration of SMC migration via integrin-beta(3).
Kanzaki
Tetsuto
T
Department of Internal Medicine, Kohnodai Hospital, National Center of Neurology and Psychiatry, 1-7-1 Kohnodai, Ichikawa City 272-8516, Japan. kanzaki@intmed02.m.chiba-u.ac.jp
Otabe
Masako
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001011:Aorta; D000077214:Becaplermin; D002352:Carrier Proteins / Q000008:administration & dosage / Q000032:analysis / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D007150:Immunohistochemistry; D039661:Integrin beta3 / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D039661:Integrin beta3; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin