| Project/Area Number |
12671582
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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 |
Obstetrics and gynecology
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| Research Institution | Tokyo Medical & Dental University |
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Principal Investigator |
KOI Hideki Tokyo Medical & Dental University, Graduate School, Assistant Professor, 大学院・医歯学総合研究科, 助手 (20280969)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Yasufumi Tokyo Medical & Dental University, Graduate School, Associate Professor, 大学院・医歯学総合研究科, 講師 (80242197)
KUBOTA Toshiro Tokyo Medical & Dental University, Graduate School, Associate Professor, 大学院・医歯学総合研究科, 助教授 (50126223)
ASO Takeshi Tokyo Medical & Dental University, Graduate School, Professor, 大学院・医歯学総合研究科, 教授 (60093176)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | thrombin / thrombin receptor / trouhoblast / invasion / matrix metalloproteinase / extravillous trophoblast / Protease-activating receptor / placenta / 栄養膜細胞 / 増殖と分化 / matriz metalloproteinase / protease-activated receptor / prothrombinase / 絨毛外栄養膜 / 脱落膜細胞 |
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| Research Abstract |
We analyzed the functional expression of protease-activating receptors, especially thrombin receptors, in extravillous trophoblast cells in the process of trophoblast invasion and placentation with the approval by the ethical committee and informed consents by the patients. PAR1, PAR2 and PAR3 are expressed in cultured extravillous trophoblast (EVT) and in situ in 18-20 week old placental syncytiotrophoblast and invasive trophoblasts. Thrombin, but not the PAR2 agonist peptide SLIGKV, inhibited proliferation in cultured EVTs, although both agonists simulated phosphoinositide hydrolysis and EVT invasion through Matrigel barriers. Moreover, thrombin increased the production of active-form MMP2 through the activation of pro-MMP2 by MT1MMP on the cell surface, which was up regulated by thrombin in cultured EVTs. These findings support a role of PAR1, and potentially PAR2 and PAR3, in the invasive phase of human placentation and the possibility that thrombin may be a regulatory factor of trophoblast differentiation from proliferate EVTs to invasive EVTs. Moreover, our data showed a novel procoagulant fgl2 was expressed in cultured EVTs and that they had a prothrombinase activity in vitro. These findings suggest that overproduction of thrombin at the invasive situ in placenta might cause the adverse consequences of pregnancy including abortion and preterm delivery by the formation of blood clots and production of excess amount of MMPs and destruction of extracellular matrix of decidua if prothrombinase activity of EVT is too much increased. Our present study indicated a regulatory role of thrombin, protease-activating receptors and fgl2 in the process of placentation and trophoblast differentiation
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