Kypreos K E, Nugent M A, Sonenshein G E
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
Cell Growth Differ. 1998 Sep;9(9):723-30.
Basic fibroblast growth factor (bFGF), a member of the fibroblast growth factor family, potently induces increased vascular smooth muscle cell (SMC) proliferation and decreased expression of type I collagen. Recently, our laboratory demonstrated that, in bovine vascular SMCs, expression of B-myb, a member of the myb gene family, is dependent upon cellular growth state and that B-myb decreases alpha1(I) collagen promoter activity in transient transfection assays. Nuclear run-off analysis indicated that the decrease in alpha1(I) collagen mRNA level seen upon bFGF treatment was due to a decline in the rate of alpha1(I) procollagen 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 bovine aortic SMCs caused an increase in B-myb mRNA levels. Ectopic expression of B-myb decreased endogenous alpha1(I) collagen mRNA levels. Importantly, introduction of a B-myb antisense oligonucleotide prevented the drop in the alpha1(I) collagen mRNA levels seen upon treatment with bFGF. Together, these results indicate that B-myb mediates signals leading to the decreased rate of alpha1(I) collagen gene transcription caused by bFGF.
碱性成纤维细胞生长因子（bFGF）是成纤维细胞生长因子家族的一员，能有效诱导血管平滑肌细胞（SMC）增殖增加，并降低I型胶原蛋白的表达。最近，我们实验室证明，在牛血管平滑肌细胞中，myb基因家族成员B-myb的表达取决于细胞生长状态，并且在瞬时转染实验中，B-myb会降低α1（I）胶原蛋白启动子活性。核转录分析表明，bFGF处理后α1（I）胶原蛋白mRNA水平的降低是由于α1（I）前胶原基因转录速率下降所致。因此，我们研究了B-Myb在bFGF下调I型胶原蛋白基因表达中的潜在作用。通过Northern印迹分析，我们发现用bFGF处理牛主动脉平滑肌细胞会导致B-myb mRNA水平升高。B-myb的异位表达降低了内源性α1（I）胶原蛋白mRNA水平。重要的是，引入B-myb反义寡核苷酸可防止bFGF处理后α1（I）胶原蛋白mRNA水平的下降。这些结果共同表明，B-myb介导了导致bFGF引起的α1（I）胶原蛋白基因转录速率降低的信号。
