Kisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cells.
Kisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cells.
复制标题
DOI：
10.1371/journal.pone.0099680
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Katz AA
中科院分区：
文献类型：
--
作者：
Francis VA;Abera AB;Matjila M;Millar RP;Katz AA
绒毛外滋养细胞侵入子宫壁的精确调节是成功妊娠的关键过程。Kisspeptin（KP）已显示出抑制癌细胞转移和胎盘滋养层细胞迁移。在这项研究中，原代培养的第一个三个月的人滋养层细胞已被用于研究的侵袭和血管生成相关基因的调节KP。从妊娠早期胎盘中分离滋养层细胞，并通过细胞角蛋白-7免疫染色确认其身份。实时定量RT-PCR显示，原代滋养层细胞比滋养层细胞系HTR 8 Svneo表达更高水平的GPR 54（KP受体）和KP mRNA。此外，滋养层细胞也表达较高的GPR 54和KP蛋白水平。用KP处理原代滋养层细胞诱导ERK 1/2磷酸化，而用KP拮抗剂共处理细胞几乎完全阻断ERK 1/2的激活，并证明KP通过其同源GPR 54受体可以激活滋养层细胞中的ERK 1/2。在划痕迁移试验中，KP降低了滋养层细胞的迁移能力。实时荧光定量RT-PCR结果显示，KP处理降低了基质金属蛋白酶1、2、3、7、9、10、14和VEGF-A的表达，增加了基质金属蛋白酶组织抑制因子1和3的表达。这些结果表明，KP可以通过抑制细胞迁移和下调金属蛋白酶系统和VEGF-A来抑制早孕滋养层细胞的侵袭。
The precise regulation of extravillous trophoblast invasion of the uterine wall is a key process in successful pregnancies. Kisspeptin (KP) has been shown to inhibit cancer cell metastasis and placental trophoblast cell migration. In this study primary cultures of first trimester human trophoblast cells have been utilized in order to study the regulation of invasion and angiogenesis-related genes by KP. Trophoblast cells were isolated from first trimester placenta and their identity was confirmed by immunostaining for cytokeratin-7. Real-time quantitative RT-PCR demonstrated that primary trophoblast cells express higher levels of GPR54 (KP receptor) and KP mRNA than the trophoblast cell line HTR8Svneo. Furthermore, trophoblast cells also expressed higher GPR54 and KP protein levels. Treating primary trophoblast cells with KP induced ERK1/2 phosphorylation, while co-treating the cells with a KP antagonist almost completely blocked the activation of ERK1/2 and demonstrated that KP through its cognate GPR54 receptor can activate ERK1/2 in trophoblast cells. KP reduced the migratory capability of trophoblast cells in a scratch-migration assay. Real-time quantitative RT-PCR demonstrated that KP treatment reduced the expression of matrix metalloproteinase 1, 2, 3, 7, 9, 10, 14 and VEGF-A, and increased the expression of tissue inhibitors of metalloproteinases 1 and 3. These results suggest that KP can inhibit first trimester trophoblast cells invasion via inhibition of cell migration and down regulation of the metalloproteinase system and VEGF-A.
登录
查看更多内容
DOI：
10.1530/joe-12-0091
发表时间：
2012-07
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Cartwright JE;Williams PJ
通讯作者：
Williams PJ
DOI：
10.1073/pnas.0609025103
发表时间：
2006-12-05
影响因子：
11.1
作者：
Galaup, Ariane;Cazes, Aurelie;Germain, Stephane
通讯作者：
Germain, Stephane
影响因子：
8.2
作者：
Hiden, Ursula;Bilban, Martin;Desoye, Gernot
通讯作者：
Desoye, Gernot
影响因子：
3.8
作者：
Roseweir, A. K.;Katz, A. A.;Millar, R. P.
通讯作者：
Millar, R. P.
DOI：
10.1034/j.1600-0897.2002.01151.x
发表时间：
2002-10-01
影响因子：
3.6
作者：
Karmakar, S;Das, C
通讯作者：
Das, C