Down-regulation of CCR7 via AKT pathway and GATA2 inactivation suppressed trophoblast migration and invasion in recurrent spontaneous abortion
Down-regulation of CCR7 via AKT pathway and GATA2 inactivation suppressed trophoblast migration and invasion in recurrent spontaneous abortion
复制标题
通过 AKT 通路下调 CCR7 和 GATA2 失活可抑制复发性自然流产中的滋养层迁移和侵袭。
DOI：
10.1093/biolre/ioz172
复制
发表时间：
2020-02-01
影响因子：
3.6
通讯作者：
Du, Yanzhi
中科院分区：
文献类型：
--
作者：
Luan, Xiaorui;Li, Shang;Du, Yanzhi
趋化因子-C受体7（CCR 7）导致反复自然流产（RSA）滋养细胞迁移和侵袭异常的潜在机制尚不清楚。CCR 7被认为对迁移和入侵至关重要，并与流产风险有关。然而，CCR 7在RSA中的功能作用尚未完全了解。我们的研究发现，与健康对照组相比，RSA患者绒毛中CCR 7 mRNA和蛋白丰度显著降低。CCR 7的敲除导致了在JEG和JEG-3细胞中的迁移和侵袭的显著减少。同时，CCR 7作为AKT通路的上游因子，促进GATA 2的表达，促进滋养细胞迁移，并通过MMP 2侵袭。值得注意的是，与对照组相比，RSA的人绒毛标本中CCR 7丰度的降低与AKT的磷酸化以及GATA 2和MMP 2的丰度呈正相关。CCL 19是CCR 7的配体，通过激活RSA中CCR 7介导的通路的失调而促进滋养细胞迁移和侵袭。我们认为CCR 7及其下游因子可能是RSA发病的重要机制。
The underlying mechanism of the chemokine-C receptor 7 (CCR7) that leads to aberrant trophoblast migration and invasion in recurrent spontaneous abortion (RSA) remains unknown. CCR7 is considered crucial for migration and invasion and has been associated with the risk of miscarriage. However, the functional role of CCR7 in RSA is not fully understood. Our study found that CCR7 mRNA and protein abundance were significantly decreased in the villous from RSA patients compared with healthy controls. Knockdown of CCR7 caused a significant reduction of migration and invasion in JAR and JEG-3 cells. Meanwhile, CCR7 functioned as a positive upstream factor of the AKT pathway contributing to the expression of GATA2, promoting trophoblast migration, and invasion via MMP2. Notably, a decreased abundance of CCR7 was positively correlated with the phosphorylation of AKT and with an abundance of GATA2 and MMP2 in human villous specimens of RSA compared with the control group. CCL19, a ligand of CCR7, could promote trophoblast migration and invasion by activating the deregulation of the CCR7-mediated pathway in RSA. We are convinced that CCR7 and its downstream factors may be possible mechanisms for the pathogenesis of RSA.Summary SentenceDown-regulation of CCR7 is involved in the development of RSA.