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.