Role of thrombospondin-1-derived peptide, 4N1K, in FGF-2-induced angiogenesis.
Angiogenesis involves proliferation of capillary endothelial cells and formation of lumen-containing tube-like structures. A recently established murine brain capillary endothelial cell line, IBE, can either proliferate or form tube-like structures (i.e., differentiate) in response to fibroblast growth factor-2 (FGF-2), dependent on the culture conditions. The 4N1K peptide (KRFYVVMWKK), which is derived from the C-terminal cell-binding domain of thrombospondin-1 (TSP-1), inhibited tube formation, but not proliferation of IBE cells. Polyclonal antibodies against 4N1K blocked TSP-1-induced inhibition of tube formation by IBE cells. 4N1K inhibited tyrosine phosphorylation of focal adhesion kinase and FGF-2-stimulated tyrosine phosphorylation of phospholipase C-gamma in tube-forming, but not proliferating, IBE cells. The peptide also inhibited FGF-2-induced neovascularization in mouse cornea. Our results indicate that TSP-1 may exert its inhibitory effects on angiogenesis via the C-terminal cell-binding domain containing the 4N1K sequence by inhibiting tube formation by endothelial cells.
Kanda
S
S
Department of Urology, Nagasaki University School of Medicine, Nagasaki, Japan.
Shono
T
T
Tomasini-Johansson
B
B
Klint
P
P
Saito
Y
Y
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009024:Morphogenesis / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D009842:Oligopeptides / Q000502:physiology*; D019700:Thrombospondin 1 / Q000502:physiology*
C120273:4N1K peptide; D009842:Oligopeptides; D019700:Thrombospondin 1; D016222:Fibroblast Growth Factor 2