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 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.
Kypreos
K E
KE
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
Nugent
M A
MA
Sonenshein
G E
GE
D000818:Animals; D002417:Cattle; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes / Q000187:drug effects / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011347:Procollagen / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D011347:Procollagen; D012333:RNA, Messenger; D015534:Trans-Activators; D016222:Fibroblast Growth Factor 2; D003094:Collagen