Activin A as a critical mediator of capillary formation: interaction with the fibroblast growth factor action

Endocr J. 2007 Apr;54(2):311-8. doi: 10.1507/endocrj.k06-222. Epub 2007 Mar 23.


The present study was conducted to elucidate the role of activin A in capillary formation. When bovine aortic endothelial cells (BAEC) were cultured in a collagen gel, basic fibroblast growth factor (FGF-2) induced tube formation. Activin A also induced tube formation and the addition of two factors together was more effective. BAEC produced both FGF-2 and activin A as autocrine factors. Exogenous FGF-2 did not affect the production of activin A but instead upregulated the type II activin receptor. On the other hand, activin A increased the expression of FGF-2 as well as the FGF receptor. Most importantly, when the action of endogenous activin A was blocked by adding follistatin, the tubulogenic action of FGF-2 was nearly completely inhibited. Activin-induced tubulogenesis was markedly inhibited by overexpression of Smad7, an inhibitory Smad. Similarly, an inhibitor of p44/42 mitogen-activated protein (MAP) kinase attenuated the activin-mediated tubulogenesis, whereas an inhibitor of p38 MAP kinase had no effect. These results indicate that FGF-2 and activin A enhance their signals each other in BAEC, and endogenous activin A is critical for FGF-2-induced capillary formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type II / metabolism
  • Activins / metabolism
  • Activins / pharmacology
  • Activins / physiology*
  • Animals
  • Aorta / cytology
  • Aorta / drug effects
  • Aorta / metabolism
  • Capillaries / physiology*
  • Cattle
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / physiology*
  • Flavonoids / pharmacology
  • Humans
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology*
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Recombinant Proteins / pharmacology
  • Smad7 Protein / genetics
  • Smad7 Protein / pharmacology
  • Transfection


  • Flavonoids
  • Recombinant Proteins
  • Smad7 Protein
  • activin A
  • Fibroblast Growth Factor 2
  • Activins
  • Receptor, Fibroblast Growth Factor, Type 1
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Activin Receptors, Type II
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one