Hepatocyte growth factor (HGF) is reported to be down-regulated in pregnancy complications like intrauterine growth retardation and preeclampsia, which are associated with abnormal trophoblast migration/invasion. In this study, role of HGF and associated signaling pathways has been investigated in HTR-8/SVneo trophoblastic cells migration/invasion under normoxia (20% O₂) and hypoxia (2% O₂). HTR-8/SVneo cells exposed to hypoxia showed increase in migration and invasion as compared to cells incubated under normoxic conditions. The migration/invasion under both normoxic and hypoxic conditions was further enhanced after treatment with HGF. Subsequent to treatment with HGF, a significant increase in expression of MMP2 & MMP3 under normoxia and MMP1 & MMP9 under hypoxia was observed. Treatment of HTR-8/SVneo cells with HGF under hypoxia also led to decrease in TIMP1. Treatment of the cells with HGF led to activation of mitogen activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. Inhibition of MAPK by U0126 and PI3K by LY294002 led to concomitant decrease in the HGF-mediated migration/invasion of HTR-8/SVneo cells. HGF treatment under hypoxia also led to a significant increase in hypoxia inducible factor (HIF-1α) expression. Additionally, inhibition of HIF-1α by siRNA led to decrease in HGF-mediated migration of HTR-8/SVneo cells under hypoxic conditions. Inhibition of HGF activated MAPK and PI3K signaling led to reduction in HIF-1α expression under hypoxia. In conclusion, HGF facilitates HTR-8/SVneo cell migration/invasion by activation of MAPK/PI3K signaling pathways and increased expression of MMPs. HIF-1α has a role in HGF-mediated increase in migration under hypoxic conditions.

中文翻译：

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HGF 通过 MAPK 和 PI3K 通路增加 HIF-1α 表达来调节 HTR-8/SVneo 滋养层细胞在缺氧条件下的迁移/侵袭。

据报道，肝细胞生长因子 (HGF) 在妊娠并发症中下调，如宫内发育迟缓和先兆子痫，这与异常滋养层迁移/侵袭有关。在本研究中，研究了 HGF 和相关信号通路在常氧 (20% O ₂ ) 和缺氧 (2% O _{2 ) 下 HTR-8/SVneo 滋养层细胞迁移/侵袭中的作用}）。与在常氧条件下孵育的细胞相比，暴露于缺氧的 HTR-8/SVneo 细胞显示出迁移和侵袭的增加。在用 HGF 治疗后，在常氧和低氧条件下的迁移/侵袭进一步增强。在用 HGF 处理后，观察到在常氧下 MMP2 和 MMP3 的表达显着增加，在缺氧下观察到 MMP1 和 MMP9 的表达显着增加。在缺氧条件下用 HGF 处理 HTR-8/SVneo 细胞也导致 TIMP1 减少。用 HGF 处理细胞导致有丝分裂原活化蛋白激酶 (MAPK) 和磷脂酰肌醇 3-激酶 (PI3K) 信号通路的激活。U0126 对 MAPK 的抑制和 LY294002 对 PI3K 的抑制导致 HGF 介导的 HTR-8/SVneo 细胞迁移/侵袭的同时减少。缺氧条件下的 HGF 治疗也导致缺氧诱导因子 (HIF-1α) 表达显着增加。此外，siRNA 对 HIF-1α 的抑制导致 HGF 介导的 HTR-8/SVneo 细胞在缺氧条件下的迁移减少。抑制 HGF 激活的 MAPK 和 PI3K 信号传导导致缺氧条件下 HIF-1α 表达降低。总之，HGF 通过激活 MAPK/PI3K 信号通路和增加 MMPs 的表达来促进 HTR-8/SVneo 细胞迁移/侵袭。HIF-1α 在缺氧条件下 HGF 介导的迁移增加中起作用。总之，HGF 通过激活 MAPK/PI3K 信号通路和增加 MMPs 的表达来促进 HTR-8/SVneo 细胞迁移/侵袭。HIF-1α 在缺氧条件下 HGF 介导的迁移增加中起作用。总之，HGF 通过激活 MAPK/PI3K 信号通路和增加 MMPs 的表达来促进 HTR-8/SVneo 细胞迁移/侵袭。HIF-1α 在缺氧条件下 HGF 介导的迁移增加中起作用。