S. Naito et al., ETS-1 IS AN EARLY RESPONSE GENE ACTIVATED BY ET-1 AND PDGF-BB IN VASCULAR SMOOTH-MUSCLE CELLS, American journal of physiology. Cell physiology, 43(2), 1998, pp. 472-480
Ets-1 is a transcription factor that activates expression of matrix-de
grading proteinases such as collagenase and stromelysin. To study the
control of ets-1 gene expression in rat vascular smooth muscle cells (
VSMC), cells were exposed to factors known to regulate VSMC migration
and proliferation. Platelet-derived growth factor-BB (PDGF-BB), endoth
elin-1 (ET-1), and phorbol 12-myristate 13-acetate (PMA) induced a dos
e-dependent expression of ets-1 mRNA. These effects were abrogated by
inhibition of protein kinase C (PKC) by H-7 or chronic PMA treatment.
Ets-1 mRNA was superinduced by PDGF-BB and ET-1 in the presence of cyc
loheximide. The chelation of intracellular Ca2+ by 1,2-bis( 2-aminophe
noxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester and the dep
letion of endoplasmic reticulum intracellular Ca2+ concentration ([Ca2
+](i)) by thapsigargin inhibited PDGF-BB- and ET-1-induced ets-1 mRNA,
whereas ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraace
tic acid had no effect. However, [Ca2+](i) release alone was not suffi
cient to increase ets-1 mRNA. Forskolin blocked ET-1-, PDGF-BB-, and P
MA-induced Ets-1 mRNA, as well as inositol phosphate formation, consis
tent with an effect through impairment of PKC activation, inhibitors o
f ets-1 gene expression, such as H-7 and herbimycin A, inhibited the E
T-1 induction of collagenase I mRNA. We propose that ets-1 may be an i
mportant element in the orchestration of matrix proteinase expression
and of vascular remodeling after arterial injury.