Ke. Kypreos et al., BASIC FIBROBLAST GROWTH FACTOR-INDUCED DECREASE IN TYPE-I COLLAGEN GENE-TRANSCRIPTION IS MEDIATED BY B-MYB, Cell growth & differentiation, 9(9), 1998, pp. 723-730
Basic fibroblast growth factor (bFGF), a member of the fibroblast grow
th factor family, potently induces increased vascular smooth muscle ce
ll (SMC) proliferation and decreased expression of type I collagen. Re
cently, our laboratory demonstrated that, in bovine vascular SMCs, exp
ression of B-myb, a member of the myb gene family, is dependent upon c
ellular growth state and that B-myb decreases alpha 1(I) collagen prom
oter activity in transient transfection assays, Nuclear run-off analys
is indicated that the decrease in alpha 1(I) collagen mRNA level seen
upon bFGF treatment was due to a decline in the rate of alpha 1(I) pro
collagen gene transcription, Thus, we investigated the potential role
of B-Myb in the down-regulation of type I collagen gene expression by
bFGF, Using Northern blot analysis, we found that bFGF treatment of bo
vine aortic SMCs caused an increase in B-myb mRNA levels. Ectopic expr
ession of B-myb decreased endogenous alpha 1(I) collagen mRNA levels.
Importantly, introduction of a B-myb antisense oligonucleotide prevent
ed the drop in the alpha 1(I) collagen mRNA levels seen upon treatment
with bFGF, Together, these results indicate that B-myb mediates signa
ls leading to the decreased rate of alpha 1(I) collagen gene transcrip
tion caused by bFGF.