BASIC FIBROBLAST GROWTH FACTOR-INDUCED DECREASE IN TYPE-I COLLAGEN GENE-TRANSCRIPTION IS MEDIATED BY B-MYB

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.