F. Bulens et al., HORMONAL-REGULATION OF THE EXPRESSION OF FIBRINOLYTIC COMPONENTS IN HT1080 FIBROSARCOMA AND ENDOTHELIAL-CELLS, Fibrinolysis & proteolysis, 11(1), 1997, pp. 57-63
The effects of the synthetic glucocorticoid dexamethasone (DEX) and of
all-trans-retinoic acid (RA) on the expression of tissue-type plasmin
ogen activator (t-PA), urokinase-type plasminogen activator (u-PA), an
d the plasminogen activator inhibitor (PAI)-1 were investigated in the
HT1080 fibrosarcoma cell line and in human umbilical vein endothelial
(HUVE) cells. DEX significantly reduced the u-PA steady state mRNA le
vel in HT1080 cells to 0.41+/-0.08-fold control. It induced the t-PA t
ranscript 2.2+/-0.36-fold and the 2.8 and 3.4 kb PAI-1 transcripts 2.5
+/-0.13-fold and 2.8+/-0.48-fold, respectively. RA increased both PAI-
1 transcripts to a minor but significant extent (1.3+/-0.03-fold and 1
.2+/-0.03-fold), and the t-PA and u-PA transcripts more strongly (11+/
-0.4-fold and 2.1+/-0.02-fold). When added together, DEX enhanced the
induction of t-PA mRNA by RA to 34+/-1.5-fold, inhibited the RA-mediat
ed induction of u-PA mRNA to 0.85+/-0.02-foId control, and further inc
reased the levels of the 2.8 and 3.4 kb PAI-1 transcripts to 3.6+/-0.1
3-fold and 5.0+/-0.05-fold, respectively. The secretion of the corresp
onding antigens in the conditioned medium paralleled the changes in mR
NA. The effects of DEX and RA were abolished by simultaneous treatment
with cycloheximide, suggesting that they required protein synthesis.
In HUVE cell culture only a minor effect on t-PA-related antigen secre
tion was observed when DEX was added alone (1.2+/-0.02-fold), but DEX
increased the induction by RA from 6.2+/-0.1-fold to 9.6+/-0.15-fold.
In contrast, DEX and RA, alone or in combination, had very little or n
o effect on the generation of PAI-1-related antigen (maximally 1.2+/-0
.4-fold). It is concluded that the glucocorticoid and the RA signal tr
ansduction pathways can interact in a complex manner resulting in a di
fferential regulation of the fibrinolytic parameters.