IGF-1 Regulates Migration and Angiogenesis of Human Endothelial Cells

摘要

References(2) Cited-By(43) Recent studies revealed favorable para- and/or autocrine effects of IGF-1 in the pathogenesis 'of diabetic complications. On the other hand, hyperglycemia is a risk factor for the development of 'diabetic vascular complications. In this study we examined the effects of high glucose and/or IGF-1 on 'cell migration and angiogenesis (tubular formation) by using human endothelial cells (EC) in vitro. First 'we examined cell migration by the two-chamber method. Chronic treatment with a high concentration 'of D-glucose strongly stimulated the cell migration, which was mimicked by PMA, a protein kinase C (PKC) agonist. The cell migration was also induced by IGF-1. The glucose-induced cell migration was blocked by PKC inhibitor, H7. IGF-1-induced cell migration was not blocked by PD98059, MAPK/ERK kinase (MEK) inhibitor or wortmannin, a phosphatidylinositol (PI) 3-kinase inhibitor. Next we examined the effects of high glucose and/or IGF-1 on the tubular formation of EC. The tubular formation was induced only when the cells were exposed to a combination of high glucose and IGF-1. The tubular formation was blocked by MEK inhibitor and PI 3-kinase inhibitor but not by PKC inhibitor. These results indicate that hyperglycemia and IGF-1, respectively, stimulate the EC migration, and tubular formation is induced by a combination of IGF-1 and hyperglycemia.