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(Circulation Research. 1996;79:263-270.)
© 1996 American Heart Association, Inc.

Articles

Heparin-Binding Epidermal Growth Factor-Like Growth Factor Regulates Fibroblast Growth Factor-2 Expression in Aortic Smooth Muscle Cells

Kimberly A. Peifley, Gregory F. Alberts, Debbie K.W. Hsu, Sheau-Line Y. Feng, Jeffrey A. Winkles

the Department of Molecular Biology (K.A.P., G.F.A., D.K.W.H., S.-L.Y.F., J.A.W.), Holland Laboratory, American Red Cross, Rockville, Md, and the Department of Biochemistry and Molecular Biology (J.A.W.), George Washington University Medical Center, Washington, DC.

Correspondence to Dr Jeffrey A. Winkles, Department of Molecular Biology, Holland Laboratory, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855. E-mail winkles@hlsun.red-cross.org.

Heparin-binding epidermal growth factor–like growth factor (HB-EGF) is a vascular smooth muscle cell (SMC) mitogen and chemotactic factor that is expressed by endothelial cells, SMCs, monocytes/macrophages, and T lymphocytes. Both the membrane-anchored HB-EGF precursor and the secreted mature HB-EGF protein are biologically active; thus, HB-EGF may stimulate SMC growth via autocrine, paracrine, and juxtacrine mechanisms. In the present study, we report that HB-EGF treatment of serum-starved rat aortic SMCs can induce fibroblast growth factor (FGF)-2 (basic FGF) gene expression but not FGF-1 (acidic FGF) gene expression. Increased FGF-2 mRNA expression is first detectable at 1 hour after HB-EGF addition, and maximal FGF-2 mRNA levels, corresponding to an 46-fold level of induction, are present at 4 hours. The effect of HB-EGF on FGF-2 mRNA levels appears to be mediated primarily by a transcriptional mechanism and requires de novo synthesized proteins. HB-EGF induction of FGF-2 mRNA levels can be inhibited by treating cells with the anti-inflammatory glucocorticoid dexamethasone or the glycosaminoglycan heparin. Finally, Western blot analyses indicate that HB-EGF–treated SMCs also produce an increased amount of FGF-2 protein. These results indicate that HB-EGF expressed at sites of vascular injury or inflammation in vivo may upregulate FGF-2 production by SMCs.

Key Words: heparin-binding epidermal growth factor–like growth factor • smooth muscle cell • fibroblast growth factor • dexamethasone • heparin

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