Modulation by bovine angiogenin of tubular morphogenesis and expression of plasminogen activator in bovine endothelial cells

Biochem Biophys Res Commun. 1995 Jun 15;211(2):476-83. doi: 10.1006/bbrc.1995.1838.


Angiogenin is a potent angiogenic molecule in the chick chorioallantoic membrane assay and rabbit corneal assay. However, no angiogenic activity has been reported in in vitro system. In this study, we isolated and purified angiogenin from bovine milk, and the biological effect of the bovine angiogenin on bovine endothelial cells was examined in in vitro angiogenesis models. Bovine angiogenin significantly stimulated both cell migration and formation of tube-like structures in the collagen gel by bovine aortic endothelial cells. Angiogenin at 10-100 ng/ml stimulated about 2-fold higher the tube formation when basic fibroblast growth factor (bFGF) at 10 ng/ml stimulated about 3-fold over the control. Tubular morphogenesis stimulated by bFGF or angiogenin was almost completely blocked in the presence of aprotinin, an inhibitor of serine proteases. Angiogenin up-regulated both mRNA level and activity of urokinase type plasminogen activator, a key mediator of angiogenesis. Moreover, both bFGF and bovine angiogenin induced a marked increase of c-fos mRNA level at 30 min after stimulation. These novel effects of bovine angiogenin are to be discussed in relation to its structure specificity.

MeSH terms

  • Allantois
  • Angiogenesis Inducing Agents / pharmacology
  • Animals
  • Aorta
  • Cattle
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chick Embryo
  • Chorion
  • Cornea / drug effects
  • Cornea / physiology
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Female
  • Fibroblast Growth Factor 2 / pharmacology*
  • Gene Expression / drug effects
  • Gene Expression / physiology*
  • Genes, fos
  • Genes, jun
  • Humans
  • Milk
  • Morphogenesis / drug effects
  • Neovascularization, Pathologic*
  • Proteins / isolation & purification
  • Proteins / pharmacology*
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Rabbits
  • Recombinant Proteins / pharmacology
  • Ribonuclease, Pancreatic*
  • Urokinase-Type Plasminogen Activator / biosynthesis*


  • Angiogenesis Inducing Agents
  • Proteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Recombinant Proteins
  • Fibroblast Growth Factor 2
  • angiogenin
  • Ribonuclease, Pancreatic
  • Urokinase-Type Plasminogen Activator