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C-myb, but not B-myb, Upregulates Type I Collagen Gene Expression in Human Fibroblasts.
- Source :
-
Journal of Investigative Dermatology . Feb99, Vol. 112 Issue 2, p191-196. 6p. 4 Black and White Photographs, 3 Graphs. - Publication Year :
- 1999
-
Abstract
- C-myb and B-myb belong to the myb family of transcription factors. We have shown previously that c-myb is deregulated in fibroblasts from systemic sclerosis (scleroderma) patients relative to normal fibroblasts. Scleroderma fibroblasts are known to express elevated levels of collagen genes and transforming growth factor β is known to be a pro-fibrotic cytokine and to induce transcription of type I collagen genes. We have therefore investigated the role of c-myb and B-myb in the regulation of type I collagen genes in response to transforming growth factor β in normal human fibroblasts. We show that, in these cells, transforming growth factor β treatment induces c-myb as well as collagen α1(I) and α2(I) gene expression, but not B-myb. Furthermore we demonstrate by co-transfection assays that c-myb can upregulate α1(I) and α2(I) collagen promoters by 6–10-fold whereas B-myb is inactive. The activity of c-myb on both type I collagen promoters requires a functional c-myb DNA binding domain suggesting a direct interaction between c-myb and these promoters. Indeed c-myb is active also on a 500 bp fragment of the α2(I) collagen promoter and can bind to this fragment in electrophoretic mobility shift assays. Finally, we show that anti-c-myb anti-sense treatment reduces α1(I) and to a lesser extent α2(I) collagen gene expression. These data strongly suggest that c-myb, but not B-myb, plays a direct role in the upregulation of type I collagen gene expression in response to transforming growth factor β. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GENE expression
*TRANSCRIPTION factors
*FIBROBLASTS
*COLLAGEN
Subjects
Details
- Language :
- English
- ISSN :
- 0022202X
- Volume :
- 112
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Investigative Dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 5167122
- Full Text :
- https://doi.org/10.1046/j.1523-1747.1999.00485.x