Inhibition of vascular endothelial cell growth by activin-A.
The demonstration of type 2 activin receptor expression in human umbilical vein endothelial cells prompted an investigation of the effects of the activin/inhibin family of hormones on vascular endothelial cell growth. Recombinant activin-A inhibited [3H]methylthymidine uptake and growth of a panel of endothelial cell types; recombinant inhibin-A was without effect. Affinity cross-linking studies demonstrated the presence of type 1 and type 2 activin receptors on the surface of bovine aortic endothelial cells, while detailed analysis of type 2 activin receptor expression revealed both type 2 and type 2B activin receptor mRNA in all endothelial cell types analyzed. In addition, capillary endothelial cells were found to express activin-beta A subunit mRNA and protein, the levels of which were increased in response to transforming growth factor (TGF)-beta. Furthermore, activin-A and TGF-beta caused additive inhibition of capillary endothelial cell [3H]methylthymidine uptake. These findings implicate the activins in the regulation of endothelial cell function, and suggest that TGF-beta and activin may interact to inhibit capillary endothelial cell growth.
McCarthy
S A
SA
Imperial Cancer Research Fund Laboratories, University of Oxford, John Radcliffe Hospital, United Kingdom.
Bicknell
R
R
D029404:Activin Receptors; D028341:Activins; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D004247:DNA / Q000096:biosynthesis; D017931:DNA Primers / Q000737:chemistry; D004730:Endothelium, Vascular / Q000166:cytology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D017931:DNA Primers; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors