title: 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.
abstract: 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.
authors.affiliation: 3rd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Inaba
authors.forename: T
authors.initials: T
authors.lastname: Gotoda
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: M
authors.initials: M
authors.lastname: Shimada
authors.forename: J
authors.initials: J
authors.lastname: Ohsuga
authors.forename: S
authors.initials: S
authors.lastname: Ishibashi
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
authors.forename: N
authors.initials: N
authors.lastname: Yamada
mesh_terms: 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
chemical_list: 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