| Project/Area Number |
09670723
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | EHIME UNIVERSITY |
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Principal Investigator |
KITAMI Yutaka EHIME UNIVERSITY,EHIME UNIVERSITY HOSPITAL,ASSISTANT PROFESSOR, 医学部附属病院, 助手 (10234270)
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| Co-Investigator(Kenkyū-buntansha) |
OKURA Takafumi EHIME UNIVERSITY,EHIME UNIVERSITY HOSPITAL,ASSISTANT PROFESSOR, 医学部附属病院, 助手 (40260385)
TAKATA Yasunori EHIME UNIVERSITY,GRADUATE COURSE
NAKAMURA Michitsugu EHIME UNIVERSITY,GRADUATE COURSE
FKUOKA Tomikazu EHIME UNIVERSITY,GRADUATE COURSE
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | PDGF receptor / vascular smooth muscle cell / promoter activity / gene transcription / CCAAT-binding protein / NF-Y family / C / EBP family / gene therapy / 血小板由来成長因子β-受容体 / 5'-上流域 / 細胞増殖 / 5^1-上流域 / NF-Y |
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| Research Abstract |
Platelet-derived growth factor (PDGF) is one of major growth factors on cellular development or hypertrophy in vascular smooth muscle cells (VSMC). PDGF is known to become physiologically active when it binds to its specific receptor, alpha or beta. -Main purpose of this study is to elucidate regulatory mechanisms of PDGF n-receptor (PDGFRB) gene expression in VSMC.Functional analyses of PDGFRB gene promoter revealed that PDGFRB gene transcription is mainly regulated by two important cis-elements located at -150 through -121 (designated R30) and at -67 through -61 (CCAAT box, designated C67). DNA-binding studies indicated that NF-Y family (especially NF-YC), which belongs to one of CCAAT-binding protein families, is specifically interacted with the C67 sequence and positively regulates the transcriptional activity of the PDGFRB gene. On the other hand, R30, which contains a negative regulatory element (NRE), negatively control the gene expression under a tissue-specific manner. Further
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more, to gain a direct evidence that these cis-elements are functional active in VSMC, effects of sequence-specific "decoy" oligodeoxynucleotide (OUN) for these two sequences on intrinsic PDGFPB mRNA expression were also investigated. Either 'decoy' ODN for R30 or C67 significantly suppressed intrinsic PDGFRB mRNA expression in VSMC indicating that these two elements can act as a functional promoter and/or an upstream control element of PDGFRB gene transcription. Previously, we have also determined the importance of another CCAAT-binding family, CCAAT/enhancer-binding proteins (C/FBP) family, on the transcriptional activity of the PDGF alpha-receptor (PDGFRA) gene in VSMC.From these two studies, we strongly postulate the hypothesis that CCAAT-binding proteins including NF-Y and C/EBP play a pivotal role in the transcriptional regulation of the genes related to the vascular development or remodeling in vivo. Furthermore, CCAAT boxs and their binding factor families may become useful candidates for the gene therapy of atherosclerotic and restenotic lesions in the vessel wall. Less
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