| Project/Area Number |
14370533
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kobe University |
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Principal Investigator |
MARUO Takeshi Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (60135811)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUO Hiroya Kobe University, School of Medicine, Professor, 医学部, 教授 (60229432)
NAKABAYASHI Koji Kobe University, Graduate School of Medicine, Assistant, 大学院・医学系研究科, 助手 (80362789)
佐藤 朝臣 神戸大学, 医学部附属病院, 助手 (90314484)
武木田 茂樹 神戸大学, 大学院・医学系研究科, 助手 (60324927)
中後 聡 神戸大学, 医学部附属病院, 講師 (50283891)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥10,500,000 (Direct Cost: ¥10,500,000)
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| Keywords | extravillous trophoblast / thyroid hormone / invasive potential / apoptosis / 細胞接着関連分子 / 初代分離培養細胞 / 細胞接着関連因子 / インテグリン / マトリックスメタロプロテイナーゼ / フィブロネクチン / マトリックスメタロプロテイナーゼ阻害因子 |
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| Research Abstract |
The present study was conducted to determine whether T_3 receptor exists in early placental extravillous trophoblasts (EVTs) and evaluate the influence of T_3 on Fas/Fas ligand expression, caspase-3, and poly (ADP-ribose) polymerase (PARP) cleavage and apoptosis in cultured early placental EVTs. Early placental EVTs expressed a 212-bp c-erb Aβ1 transcript and the T_3 receptor protein and exhibited significant levels of apoptosis in culture. Treatment with T_3 reduced the expression of Fas and Fas ligand as well as cleavage of caspase-3 and PARP and suppressed apoptosis in cultured EVTs. These results demonstrate that T_3 receptor is present in early placental EVTs and that T_3 suppresses apoptosis by down-regulating the expression of Fas and Fas ligand. Furthermore, in order to investigate the possible role of T_3 in the regulation of EVT invasion to the decidua, we have examined whether T_3 affects EVT invasive potential and the expression of matrix metalloproteinase-2 (MMP-2), MMP-3, tissue inhibitor metalloproteinase-1, fetal fibronectin (FN), and integrin α_5β_1 in cultured early placental EVTs. Matrigel invasion assay demonstrated that the treatment with T_3 significantly increased the number of cell projections of cultured EVTs. RT-PCR analysis revealed that the treatment with T_3 increased the expression of MMP-2, MMP-3, fetal FN, and integrin α_5β_1 mRNA in cultured EVTs. Immunocytochemical and Western immunoblot analysis revealed that treatment with T_3 increased the expression of MMP-2 and MMP-3 in cultured EVTs. The present results suggest that T_3 (10^<-8>_M) may play a vital role in up-regulating the invasive potential of EVTs into the decidua.
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