PDF(Pubmed)
Abstract：
BACKGROUND: Extravillous trophoblasts (EVTs) form stratified columns at the placenta-uterus interface. In the closest part to fetal structures, EVTs have a proliferative phenotype, whereas in the closest part to maternal structures, they present a migratory phenotype. During the placentation process, Connexin 40 (Cx40) participates in both the proliferation and migration of EVTs, which occurs under hypoxia. However, a possible interaction between hypoxia and Cx40 has not yet been established.
METHODS: We developed two cellular models, one with \"low Cx40\" (Jeg-3), which reflected the expression of this protein found in migratory EVTs, and one with \"high Cx40\" (Jeg-3/hCx40), which reflected the expression of this protein in proliferative cells. We analyzed the migration and proliferation of these cells under normoxic and hypoxic conditions for 24 h. Jeg-3 cells under hypoxia increased their migratory capacity over their proliferative capacity. However, in Jeg-3/hCx40, the opposite effect was induced. On the other hand, hypoxia promoted gap junction (GJ) plaque formation between neighboring Jeg-3 cells. Similarly, the activation of a nitro oxide (NO)/cGMP/PKG-dependent pathway induced an increase in GJ-plaque formation in Jeg-3 cells.
CONCLUSIONS: The expression patterns of Cx40 play a crucial role in shaping the responses of EVTs to hypoxia, thereby influencing their migratory or proliferative phenotype. Simultaneously, hypoxia triggers an increase in Cx40 gap junction (GJ) plaque formation through a pathway dependent on NO.
METHODS: We developed two cellular models, one with \"low Cx40\" (Jeg-3), which reflected the expression of this protein found in migratory EVTs, and one with \"high Cx40\" (Jeg-3/hCx40), which reflected the expression of this protein in proliferative cells. We analyzed the migration and proliferation of these cells under normoxic and hypoxic conditions for 24 h. Jeg-3 cells under hypoxia increased their migratory capacity over their proliferative capacity. However, in Jeg-3/hCx40, the opposite effect was induced. On the other hand, hypoxia promoted gap junction (GJ) plaque formation between neighboring Jeg-3 cells. Similarly, the activation of a nitro oxide (NO)/cGMP/PKG-dependent pathway induced an increase in GJ-plaque formation in Jeg-3 cells.
CONCLUSIONS: The expression patterns of Cx40 play a crucial role in shaping the responses of EVTs to hypoxia, thereby influencing their migratory or proliferative phenotype. Simultaneously, hypoxia triggers an increase in Cx40 gap junction (GJ) plaque formation through a pathway dependent on NO.
摘要：
背景：静脉滋养细胞（EVT）在胎盘-子宫界面形成分层柱。在最接近胎儿结构的部分，EVT有增殖表型,而在最接近母体结构的部分，它们呈现迁徙表型。在安置过程中，连接蛋白40（Cx40）参与EVT的增殖和迁移，这是在缺氧的情况下发生的。然而,缺氧和Cx40之间可能的相互作用尚未确定.
方法：我们开发了两种细胞模型，一个带有“低Cx40”（Jeg-3），这反映了在迁徙性EVT中发现的这种蛋白质的表达，和一个“高Cx40”（Jeg-3/hCx40），这反映了这种蛋白质在增殖细胞中的表达。我们分析了这些细胞在常氧和低氧条件下24小时的迁移和增殖。低氧条件下的Jeg-3细胞增加了它们的迁移能力，超过了它们的增殖能力。然而,在Jeg-3/hCx40中，诱导了相反的作用。另一方面,缺氧促进相邻Jeg-3细胞间缝隙连接（GJ）斑块的形成。同样，一氧化氮（NO）/cGMP/PKG依赖性途径的激活诱导了Jeg-3细胞中GJ斑块形成的增加。
结论：Cx40的表达模式在塑造EVT对缺氧的反应中起着至关重要的作用，从而影响它们的迁移或增殖表型。同时,低氧通过依赖于NO的途径引发Cx40缝隙连接（GJ）斑块形成的增加。
方法：我们开发了两种细胞模型，一个带有“低Cx40”（Jeg-3），这反映了在迁徙性EVT中发现的这种蛋白质的表达，和一个“高Cx40”（Jeg-3/hCx40），这反映了这种蛋白质在增殖细胞中的表达。我们分析了这些细胞在常氧和低氧条件下24小时的迁移和增殖。低氧条件下的Jeg-3细胞增加了它们的迁移能力，超过了它们的增殖能力。然而,在Jeg-3/hCx40中，诱导了相反的作用。另一方面,缺氧促进相邻Jeg-3细胞间缝隙连接（GJ）斑块的形成。同样，一氧化氮（NO）/cGMP/PKG依赖性途径的激活诱导了Jeg-3细胞中GJ斑块形成的增加。
结论：Cx40的表达模式在塑造EVT对缺氧的反应中起着至关重要的作用，从而影响它们的迁移或增殖表型。同时,低氧通过依赖于NO的途径引发Cx40缝隙连接（GJ）斑块形成的增加。
