Heparin-binding epidermal growth factor-like growth factor regulates fibroblast growth factor-2 expression in aortic smooth muscle cells.
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 at 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 approximately 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.
Peifley
K A
KA
Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, Md 20855, USA.
Alberts
G F
GF
Hsu
D K
DK
Feng
S L
SL
Winkles
J A
JA
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D014158:Transcription, Genetic / Q000187:drug effects
C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D006493:Heparin; D003513:Cycloheximide