Vitamin D attenuates sphingosine-1-phosphate (S1P)-mediated inhibition of extravillous trophoblast migration.
Vitamin D attenuates sphingosine-1-phosphate (S1P)-mediated inhibition of extravillous trophoblast migration.
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DOI：
10.1016/j.placenta.2017.09.009
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发表时间：
2017-12
期刊：
影响因子：
3.8
通讯作者：
Johnstone ED
中科院分区：
文献类型：
--
作者：
Westwood M;Al-Saghir K;Finn-Sell S;Tan C;Cowley E;Berneau S;Adlam D;Johnstone ED
滋养细胞入侵和母体血管重塑的失败导致妊娠并发症先兆子痫（PE）。在其他系统中，鞘脂，鞘氨醇-1-磷酸（S1 P），控制细胞迁移，因此本研究确定其对绒毛外滋养层（EVT）功能的影响。使用transwell迁移系统评估三种滋养层细胞系Swan-71、SGHPL-4和JEG 3以及原代人滋养层细胞在存在或不存在S1 P、S1 P通路抑制剂和1，25（OH）2D 3的情况下的行为。QPCR和免疫定位用于证明EVT S1 P受体表达。EVT表达S1 P受体1、2和3。S1 P抑制EVT迁移。在特异性S1 PR 2抑制剂JTE-013存在下，这种作用被消除（与单独S1 P相比p < 0.05），而用S1 R1/3抑制剂FTY 720处理则没有作用。在其他细胞类型中，S1 PR 2受维生素D调节;在这里，我们发现用1，25（OH）2D 3处理48或72小时可降低S1 PR 2（4倍; <0.05），但不降低R1和R3的表达。S1 P对1，25（OH）_2D_3诱导的细胞迁移无明显抑制作用（p < 0.05）。这项研究表明，虽然EVT表达三种S1 P受体亚型，但S1 P主要通过S1 PR 2/Gα12/13信号激活Rho，从而作为EVT迁移的有效抑制剂。重要的是，维生素D可以下调S1 PR 2的表达，从而下调S1 P的功能。我们的数据表明，维生素D缺乏，这是已知的与PE，可能有助于受损的滋养层迁移，这种情况下。鞘氨醇-1-磷酸（S1 P）控制绒毛外滋养层（EVT）迁移。通过鞘氨醇-1-磷酸受体2（S1 PR 2）控制迁移。维生素D减弱S1 PR 2的表达，因此在S1 P存在下促进EVT迁移。
Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems, the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration therefore this study determined its effect on extravillous trophoblast (EVT) function. A transwell migration system was used to assess the behaviour of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and 1,25(OH)2D3. QPCR and immunolocalisation were used to demonstrate EVT S1P receptor expression. EVTs express S1P receptors 1, 2 and 3. S1P inhibited EVT migration. This effect was abolished in the presence of the specific S1PR2 inhibitor, JTE-013 (p < 0.05 versus S1P alone) whereas treatment with the S1R1/3 inhibitor, FTY720, had no effect. In other cell types S1PR2 is regulated by vitamin D; here we found that treatment with 1,25(OH)2D3 for 48 or 72 h reduces S1PR2 (4-fold; <0.05), but not R1 and R3, expression. Moreover, S1P did not inhibit the migration of cells exposed to 1,25(OH)2D3 (p < 0.05). This study demonstrates that although EVT express three S1P receptor isoforms, S1P predominantly signals through S1PR2/Gα12/13 to activate Rho and thereby acts as potent inhibitor of EVT migration. Importantly, expression of S1PR2, and therefore S1P function, can be down-regulated by vitamin D. Our data suggest that vitamin D deficiency, which is known to be associated with PE, may contribute to the impaired trophoblast migration that underlies this condition. Sphingosine-1-Phosphate (S1P) controls extravillous trophoblast (EVT) migration. Control of migration is exerted through Sphingosine-1-Phosphate receptor 2 (S1PR2). Vitamin D attenuates the expression of S1PR2 and therefore promotes EVT migration in the presence of S1P.
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影响因子：
56.9
作者：
Lee, MJ;Van Brocklyn, JR;Hla, T
通讯作者：
Hla, T
影响因子：
4.1
作者：
Murata, N;Sato, K;Okajima, F
通讯作者：
Okajima, F
影响因子：
11.2
作者：
Lepley, D;Paik, JH;Ferrer, F
通讯作者：
Ferrer, F
影响因子：
4.8
作者：
Kon, J;Sato, K;Okajima, F
通讯作者：
Okajima, F
DOI：
10.1111/1471-0528.12071
发表时间：
2013-02-01
影响因子：
5.8
作者：
Mackay, D. F.;Smith, G. C. S.;Pell, J. P.
通讯作者：
Pell, J. P.