Activin A augments vascular endothelial growth factor activity in promoting branching tubulogenesis in hepatic sinusoidal endothelial cells.
OBJECTIVE
The production of activin A is markedly up-regulated in hepatocytes after partial hepatectomy. This factor tonically inhibits growth of hepatocytes but little is known about its effect on sinusoidal endothelial cells (SEC). In the present study, we investigated whether or not activin A affects growth and differentiation of SEC.


METHODS
Growth and survival of SEC were measured in monolayer culture. Capillary formation was studied using SEC cultured in a collagen gel.


RESULTS
SEC could not survive in the absence of vascular endothelial growth factor (VEGF). Activin A had a small effect on prevention of cell death and also enhanced anti-apoptotic action of VEGF. In addition, activin A and VEGF acted synergistically to stimulate cell growth of SEC. In the collagen gel, VEGF induced capillary formation of SEC. Activin A had little effect on branching tubulogenesis by itself but markedly enhanced tubular formation induced by VEGF. Finally, VEGF induced the expression of activin A and activin A increased the expression of VEGF receptors in cultured SEC.


CONCLUSIONS
Activin A augments VEGF activity in promoting growth and tubulogenesis of SEC.
Endo
Daisuke
D
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
Kogure
Kimitaka
K
Hasegawa
Yoshihisa
Y
Maku-uchi
Masatoshi
M
Kojima
Itaru
I
D028341:Activins / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D038681:Follistatin / Q000096:biosynthesis; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000494:pharmacology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D038681:Follistatin; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits