缺氧诱导因子-2α对滋养细胞HTR8/SVneo侵袭及血管形成的影响

Effect of Hypoxia-Inducible Factor 2 Alpha on the Invasion and Tube Formation of Extravillour Trophoblast Cell Line HTR8/SVneo

目的：研究缺氧诱导因子2α（HIF-2α）对绒膜外滋养细胞系HTR8/SVneo侵袭及血管形成的影响,并探讨其可能的信号通路。方法：建立滋养细胞缺氧模型,用Western Blot检测HIF-2α蛋白的表达、Transwell小室法检测侵袭能力、Tube formation法检测血管形成能力。同时应用HIF-2α抑制剂检测缺氧条件下HIF-2α表达抑制对绒毛膜外滋养细胞HTR8/SVneo侵袭及血管形成的影响,并检测其下游信号因子ARRDC3及PPARγ的表达。结果：缺氧（1%O2）诱导HTR8/SVneo细胞HIF-2α的表达并抑制其侵袭及血管形成能力;缺氧条件下（1%O2）,HIF-2α抑制剂抑制HTR8/SVneo细胞HIF-2α的表达,改善缺氧对HTR8/SVneo细胞侵袭及管形成的抑制,并下调ARRDC3及PPARγ的表达。结论：HIF-2α可能通过介导ARRDC3和PPARγ的表达抑制滋养细胞侵袭及血管形成,为子痫前期发病机制的研究提供了新线索。

Objective：To investigate the effect of hypoxia-inducible factor 2α（HIF-2α ）on invasion and tube-formation of extravillous trophoblast（EVT）cell line HTR8/SVneo,and to explore its potential signaling pathways.Methods：An in vitro hypoxia cell model in EVT cell lines HTR8/SVneo was established,Western Blotting was used to detect the HIF-2α expression,cell invasion was measured by transwell assay and tube formation assay was used to detect the cell angiogenic ability.In addition,we explored the effect of regulation of HIF-2α by using HIF-2α translation inhibitor on the invasion and tube formation of HTR8/SVneo and detected the expression of ARRDC3 and PPARγ.Results：Hypoxia induced the expression of HIF-2α and inhibited the invasion and tube formation of EVT trophoblasts lines HTR8/SVneo.Translation inhibitor downregulated the expression of HIF-2α ,ARRDC3 and PPARγ,and reversed the inhibition of invasion and tube formation by hypoxia in HTR-8 SV/neo cells.Conclusion：Our discovery proves that HIF-2α might be involved in the pathogenesis of PE by suppressing EVT trophoblasts lines HTR8/SVneo invasion and tube formation via inhibiting PPARγand ARRDC3 expression.