Differential effects of growth hormone and insulin-like growth factor I on human endothelial cell migration

• Published in: American Journal of Physiology: Cell Physiology 2001-05, Vol.280 (5), p.C1255-C1261
• Main Authors: Ikeo, Sachiko, Yamauchi, Keishi, Shigematsu, Satoshi, Nakajima, Koji, Aizawa, Toru, Hashizume, Kiyoshi
• Format: Article
• Language: English
• Subjects: Cell Line; Cell Movement - drug effects; Cell Movement - physiology; Endothelin-1 - pharmacology; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Enzyme Inhibitors - pharmacology; Epidermal Growth Factor - pharmacology; Human Growth Hormone - pharmacology; Humans; Indoles - pharmacology; Insulin-Like Growth Factor I - pharmacology; Maleimides - pharmacology; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Mitogen-Activated Protein Kinases - metabolism; Protein Kinase C - metabolism; Recombinant Proteins - pharmacology; Signal Transduction - drug effects; Signal Transduction - physiology; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.2001.280.5.c1255

Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, 390-8621 Japan Effects of growth hormone (GH), insulin-like growth factor I (IGF-I), and endothelin-1 (ET-1) on endothelial cell migration and the underlying molecular mechanisms were explored using a human umbilical cord endothelial cell line, ECV304 cells, in vitro. Treatment of the cells with IGF-I or ET-1, but not GH, stimulated the cell migration. Interestingly, however, ET-1-induced, but not IGF-I-induced, migration of the cells was inhibited by GH. Both ET-1 and IGF-I caused activation of mitogen-activated protein kinase (MAPK) in the cells, and GH eliminated the MAPK activation produced by ET-1 but not that produced by IGF-I. On the other hand, migration of the cells was stimulated by protein kinase C (PKC) agonist, phorbol 12-myristate 13-acetate. ET-1 promoted PKC activity, and a PKC inhibitor, GF-109203X, blocked ET-1-induced cell migration. Although GH inhibited ET-1-induced cell migration and MAPK activity, it did not block ET-1-induced PKC activation. Thus ET-1 stimulation of endothelial cell migration appears to be mediated by PKC/MAPK pathway, and GH may inhibit the MAPK activation by ET-1 at the downstream of PKC. protein kinase C; endothelin-1; Akt; phosphatidyl inositol 3'-kinase; mitogen-activated protein kinase