Cell Growth & Differentiation, Vol 2, Issue 11 531-540, Copyright © 1991 by American Association of Cancer Research

ARTICLES

Serum, phorbol ester, and polypeptide mitogens increase class 1 and 2 heparin-binding (acidic and basic fibroblast) growth factor gene expression in human vascular smooth muscle cells

JA Winkles and CG Gay
Laboratory of Molecular Biology, American Red Cross, Rockville, Maryland 20855.

Vascular smooth muscle cell proliferation is regarded as a key early event in the pathogenesis of atherosclerosis. Heparin-binding growth factor (HBGF)-1 and HBGF-2, also referred to as acidic and basic fibroblast growth factor, are potent mitogens for human vascular smooth muscle cells. These cells coexpress HBGF-1 and HBGF-2 and thus represent a vessel wall source for both polypeptides. In this report, we demonstrate that HBGF-1 and HBGF-2 expression is increased when quiescent human smooth muscle cells are treated with fetal bovine serum. The kinetics of HBGF-1 and HBGF-2 mRNA accumulation following serum treatment are distinct. In addition, HBGF-1 transcripts remain elevated for a longer time period; this may reflect the different decay rates of the HBGF-1 and HBGF-2 mRNAs. Serum-inducible HBGF-1 and HBGF-2 mRNA expression does not occur when RNA synthesis is repressed by actinomycin D but can occur in the presence of cycloheximide, an inhibitor of protein synthesis. Immunoprecipitation experiments indicate that serum treatment also increases HBGF-1 and HBGF-2 production. Smooth muscle cells treated with phorbol 12-myristate 13-acetate or certain combinations of polypeptide growth factors also express increased levels of HBGF-1 and HBGF-2 transcripts. Potential sources for these growth factors in vivo include platelets, macrophages, and T lymphocytes; thus, smooth muscle cells located at sites of vascular injury or inflammation may express elevated levels of HBGF-1 and HBGF-2.

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