Heparin-binding EGF-like growth factor synthesis by smooth muscle cells.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been previously demonstrated to be a potent mitogen for smooth muscle cells. Evidence is now presented that these cells synthesize HB-EGF as well. Cultured fetal human vascular smooth muscle cells express 2.5-kb HB-EGF mRNA. These cells also release an HB-EGF-like activity that (i) stimulates smooth muscle cell and BALB/c 3T3 cell but not endothelial cell proliferation; (ii) binds to TSK heparin affinity columns and is eluted with 0.9-1.2 M NaCl, and (iii) triggers phosphorylation of a protein with the same molecular weight as the 170-kD EGF receptor. In addition, 125I-HB-EGF can be cross-linked to the EGF receptor on fetal human vascular smooth muscle cells. These results suggest that smooth muscle cells can both synthesize and respond to HB-EGF, and that HB-EGF may therefore be involved in autocrine regulation of these cells.
Department of Surgical Research, Children's Hospital, Boston, Mass 02115.
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Higashiyama
J A
JA
Abraham
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M
Klagsbrun
D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D017077:Culture Media, Conditioned; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D006493:Heparin