Induction of sustained expression of proto-oncogene c-fms by platelet-derived growth factor, epidermal growth factor, and basic fibroblast growth factor, and its suppression by interferon-gamma and macrophage colony-stimulating factor in human aortic medial smooth muscle cells.
Vascular medial smooth muscle cells migrate, proliferate and transform to foam cells in the process of atherosclerosis. We have reported that the intimal smooth muscle cells express proto-oncogene c-fms, a characteristic gene of monocyte-macrophages, which is not normally expressed in medial smooth muscle cells. In the present study, we demonstrated that combinations of platelet-derived growth factor (PDGF)-BB and either epidermal growth factor (EGF) or fibroblast growth factor (FGF) induced high expression of c-fms in normal human medial smooth muscle cells to the level of intimal smooth muscle cells or monocyte-derived macrophages, whereas c-fms expression by PDGF-BB alone was 1/10 and both EGF and FGF had no independent effect on c-fms expression. By contrast, interferon (IFN)-gamma and macrophage colony-stimulating factor (M-CSF) suppressed the induction of c-fms expression. These results indicate that multiple growth factors and cytokines may play a role in the phenotypic transformation of medial smooth muscle cells to intimal smooth muscle cells in atherosclerotic lesions by altering c-fms expression.
Inaba
T
T
3rd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Gotoda
T
T
Harada
K
K
Shimada
M
M
Ohsuga
J
J
Ishibashi
S
S
Yazaki
Y
Y
Yamada
N
N
D001011:Aorta / Q000166:cytology; D001161:Arteriosclerosis / Q000209:etiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016236:Genes, fms / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008565:Membrane Proteins; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000254:growth & development / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000032:analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D011971:Receptors, Immunologic / Q000032:analysis; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D017539:Tunica Intima / Q000166:cytology / Q000254:growth & development; D017540:Tunica Media / Q000166:cytology / Q000254:growth & development
D016207:Cytokines; C000715470:MAS1 protein, human; D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016186:Receptor, Macrophage Colony-Stimulating Factor