Research using the primary cell culture of trophoblasts to clarify how is the differentiation of trophoblasts regulated
| Project/Area Number |
16591644
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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 | The University of Tokyo |
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Principal Investigator |
FUJII Tomoyuki The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (40209010)
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| Co-Investigator(Kenkyū-buntansha) |
KOZUMA Shiro The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (10272569)
YAMASHITA Takahiro The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (90313147)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Trophoblasts / Decidual lymphocytes / Angiogenic factor / Oxygen tension / Preeclampsia / T helper-1 / Placenta construction / Cell culture / インターロイキン-2 / 低酸素 / 妊娠中毒症 / PlGF / sFlt-1 / VEGF |
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| Research Abstract |
Sufficient cytotrophoblasts (CTs) differentiation and subsequent remodeling of maternal uterine vasculature is critical to establish uteroplacental circulation. The production of vascular endothelial growth factor (VEGF) family molecules is confirmed in placental cells including CTs. However, it is not elucidated how the differentiation of CTs along with the alteration of their function, especially VEGF system in CTs, is controlled by local environment in placenta such as oxygen tension and maternal immune cells, and how it is involved in the development of placental circulation. To address this, we explored the effect of oxygen tension and maternal immune cells on the expression of VEGF and its antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1) using a primary CT culture system. Reduced oxygen resulted in a pronounced increase in sFlt-1 production in CTs, whereas this was not the case in other placental cells. VEGF production was also stimulated by reduced oxygen in CTs but much
… More
less than sFlt-1 production. These results implicate that CTs possess a unique property to enhance sFlt-1 production under reduced oxygen, which could consequently antagonize angiogenic activity of VEGF. As for maternal immune cells, CTs pretreated with decidual lymphokine-activated killer (LAK) cells released more sFlt-1 compared with those pretreated with non-activated lymphocytes. The production of VEGF from CTs was not altered by pretreatment with either activated or non-activated decidual lymphocytes(DMCs). In preeclamptic placenta, LAK cells induced from DMCs by co-existing IL-2 may react to the CTs and enhance the release of sFlt-1 from CTs without any change of VEGF secretion. This might result in the reduction of actual angiogenic potential of the VEGF system in decidua and the placental vascular system might be compromised, which may lead to the hypoxia in placenta and hypoxia in placenta might further antagonize the placental vasculature by secreting more sFlt-1 and develop preeclampsia. Less
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Report
(3 results)
Research Products
(3 results)
