Plasminogen activator inhibitor-1 is induced in microvascular endothelial cells by a chondrocyte-derived transforming growth factor-beta.
We have previously demonstrated that a chondrocyte-derived TGF-beta inhibits spontaneous endothelial sprout formation in an in vitro model of angiogenesis (Pepper et al., J.Cell.Physiol. 146:170-179, 1991). We suggested that the inhibition might be mediated by an antiproteolytic effect. In this paper, we describe the induction of PAI-1 and PAI-1 mRNA in microvascular endothelial cells by chondrocyte conditioned medium. This effect can be significantly reduced by the addition of anti-TGF-beta antibodies to the conditioned medium, and can be mimicked by the addition of exogenous TGF-beta 1. Taken together with our previous observations, these results demonstrate that the inhibition of endothelial sprout formation occurs concomitantly with an increase in the production of PAI-1, a physiological plasminogen activator inhibitor. This suggests that TGF-beta-induced antiproteolysis is responsible for the inhibition of sprout formation.
Pepper
M S
MS
Department of Morphology, University of Geneva Medical Center, Switzerland.
Montesano
R
R
Orci
L
L
Vassalli
J D
JD
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002642:Chick Embryo; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000276:immunology / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015291:Transforming Growth Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D015849:Plasminogen Inactivators; D011506:Proteins; D012333:RNA, Messenger; D015291:Transforming Growth Factors