| Co-Investigator(Kenkyū-buntansha) |
OSUGA Jun-ichi University of Tokyo, Faculty of Medicine, Research Fellow, 医学部・附属病院, 医員
HARADA Kenji University of Tokyo, Faculty of Medicine, Research Fellow, 医学部・附属病院, 医員
ISHIBASHI Shun University of Tokyo, Faculty of Medicine, Research Associate, 医学部・附属病院, 助手 (90212919)
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| Research Abstract |
Proto-oncogene, c-fms is the gene which encodes the receptor of macrophage colony-stimulating factor (M-CSF) which regulates differentiation, maturation, and proliferation of the monocyte-macrophages. This gene locates next to the PDGF-beta receptor gene, and in the normal condition it is expressed only in the monocyte-macrophages and is not expressed in the mesenchymal cell such as vascular smooth muscle cell. These two genes regulate the specificity of those gene expression in cells without coexpressing in the normal vessel wall. We reported that both receptors are coexpressed in cells derived from atherosclerotic lesions. It was indicated that the transformation of cells, namely the foam cell formation, was stimulated through the action of both M-CSF and PDGF-beta during the atherosclerotic process. Recently, we examined the transcriptional control of the c-fms expression, and it is recognized that there are the position which suppresses the gene transcription and stimulating position in the upstream of gene, and the involvement of transcription factors of PU.1, E2A, and Id2 was reported.
In the background of the pathological reaction of the vessel wail cells, the failure of normal regulation of the gene concerning cell proliferation seemed to exist, and we considered that it was required to clarify the mechanism of proliferation and transformation of the cell in the vessel wall through these two gene expression and analysis of the regulation mechanism. By producing knockout mouse of c-fms and M-CSF overexpression mouse, we intends to clarify the pathological significance of M-CSF action in the atherosclerotic process. Then, by examining mechanism of foam cell formation in cells lucking c-fms derived from knockout mouse, we intends to clarify the significance of M-CSF/PDGF system in athorogenesis.
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