Induction of Macrophage Colony-stimulating Factor Receptor (c-fms) Expression in Vascular Medial Smooth Muscle Cells Treated with Heparin Binding Epidermal Growth Factor-like Growth Factor

Vascular smooth muscle cells migrate, proliferate, and transform to foam cells during the atherosclerotic process. We have reported that smooth muscle cells derived from the intima of atherosclerotic lesions express the proto-oncogene c- fms and a scavenger receptor, which are not normally expressed in normal medial smooth muscle cells. In the present study, we demonstrated that heparin binding epidermal growth factor-like growth factor (HB-EGF) induced the expression of c- fms and the scavenger receptor in normal human medial smooth muscle cells to the level observed in the intima. The expression of c- fms was partially inhibited by a protein kinase C inhibitor, suggesting that HB-EGF induces c- fms via pathways that are both dependent on and independent of protein kinase C. By contrast, most of the scavenger receptor induction by HB-EGF was suppressed by protein kinase C inhibitors. These results indicate that two characteristic genes of monocyte-derived macrophages were induced by HB-EGF via different mechanisms. The alteration of gene expression in response to HB-EGF may play an important role in the phenotypic change of smooth muscle cells to macrophage-like foam cells during the atherosclerotic process.