2013 Fiscal Year Final Research Report
A new therapeutic approach of preeclampsia with lysophospholipids
| Project/Area Number |
23791825
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nagoya University |
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Principal Investigator |
KOTANI Tomomi 名古屋大学, 医学部附属病院, 講師 (70359751)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 胎児発育不全 / 絨毛浸潤 / S1P / LPA |
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| Research Abstract |
The subtypes of receptors of lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) were expressed in EVT at early gestation. LPA3, S1P1 and S1P3 promoted migration of EVT, but S1P2 suppressed that in EVT cell lines. LPA induced invasion of EVT via activation of ERK, STAT-3, and Akt. S1P1 and S1P3 induced the expression of MMP-9, but S1P2 reduced it. The expression pattern of S1PR subtypes was dependent on cell density. In high cell concentration, S1P2 was mainly expressed, but S1P1 and S1P3 were dominantly expressed in low cell concentration. The antagonist of S1P2 (JTE-013) significantly induced migration of EVT. In pregnant ICR mouse, peritoneal injection of JTE-013 had no effect on the development of placenta and fetus, but injection of FTY720 (S1P1 and 3 antagonist) significantly reduced the weight of placenta and fetus, compared with control. Thus, antagonists or agonists of LPA or S1P could be a new therapeutic drug for fetal growth retardation, and preeclampsia.
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