Activin A as a critical mediator of capillary formation: interaction with the fibroblast growth factor action.
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.
Hayashi
Yoshiro
Y
Department of Anesthesiology, Gunma University Graduate School of Medicine, Japan.
Maeshima
Kyoko
K
Goto
Fumio
F
Kojima
Itaru
I
D030301:Activin Receptors, Type II / Q000378:metabolism; D028341:Activins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002196:Capillaries / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D051906:Smad7 Protein / Q000235:genetics / Q000494:pharmacology; D014162:Transfection
D005419:Flavonoids; D011994:Recombinant Proteins; D051906:Smad7 Protein; C422405:activin A; D016222:Fibroblast Growth Factor 2; D028341:Activins; D051496:Receptor, Fibroblast Growth Factor, Type 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D030301:Activin Receptors, Type II; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one