An antisense oligonucleotide to the notch ligand jagged enhances fibroblast growth factor-induced angiogenesis in vitro.
Angiogenesis, or the formation of new blood vessels, plays a central role in a number of physiologic and pathologic conditions, including wound healing, diabetic retinopathy, and solid tumor growth, and endothelial cells can be induced to mimic this process in vitro. Using a modification of the differential display method (Zimrin, A. B., Villeponteau, B., and Maciag, T. (1995) Biochem. Biophys. Res. Commun. 213, 630-638), we isolated the human homolog of the Jagged ligand for the Notch receptor from human endothelial cells exposed to fibrin and demonstrate that the Jagged transcript, but not the Notch 1 or Notch 2 transcripts, are up-regulated by fibrin. Interestingly, the addition of an antisense Jagged oligomer to bovine microvascular endothelial cells grown on a collagen gel resulted in a marked increase in invasion and tube formation in the underlying gel in response to fibroblast growth factor. In contrast, no effect was observed on vascular endothelial growth factor-induced angiogenesis under identical conditions. These data suggest that Jagged-Notch signaling is able to regulate fibroblast growth factor-induced endothelial cell migration in vitro, an early event during angiogenesis in vivo.
Zimrin
A B
AB
Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.
Pepper
M S
MS
McMahon
G A
GA
Nguyen
F
F
Montesano
R
R
Maciag
T
T
D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D018919:Neovascularization, Physiologic; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger / Q000235:genetics; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000235:genetics*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014157:Transcription Factors
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2