Activation of adenosine A2B receptor impairs properties of trophoblast cells and involves mitogen-activated protein (MAP) kinase signaling
Activation of adenosine A2B receptor impairs properties of trophoblast cells and involves mitogen-activated protein (MAP) kinase signaling
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DOI：
10.1016/j.placenta.2014.06.369
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发表时间：
2014-09-01
期刊：
影响因子：
3.8
通讯作者：
von Versen-Hoeynck, F.
中科院分区：
文献类型：
--
作者：
Darashchonak, N.;Sarisin, A.;von Versen-Hoeynck, F.
简介：滋养层浅层侵入母体螺旋动脉会导致胎盘灌注受损，并被推测与先兆子痫的病理生理学有关。缺氧是腺苷释放的有力刺激物。方法：我们研究了缺氧和 A(2B) 腺苷受体信号传导对滋养层细胞 (HTR-8/SVneo、HTR-8/SVneo、结果：与未处理的对照细胞相比，腺苷 A(2B) 受体激动剂 5-N-乙基羧酰胺腺苷 (NECA) 可减少滋养层（HTR-8/SVneo 和 BeWo）迁移 2%、8% 和 21% O-2。在所有三种 O-2 浓度下，A(2B) 腺苷受体刺激均可降低细胞外信号调节激酶 1 和 2 (ERK1/2) 以及应激激活蛋白激酶/Jun 氨基末端激酶 (SAPK/JNK) 的磷酸化。滋养层细胞中 A(2B) 腺苷受体激活后，ProMMP-2 活性、MMP-2 mRNA 水平和 hCG 水平显着降低。腺苷受体 A(2B) 刺激可降低 2% 和 8% O-2 时的 VEGF 表达，但导致 21% O-2 时的水平升高。结论：这些数据表明，A(2B) 受体激活可能会由于 MAPK 信号通路激活减少和 proMMP-2 水平降低而阻碍滋养层迁移。这些数据表明腺苷受体 An 在胎盘发育中发挥作用，并可能在先兆子痫的病理生理学中发挥作用。 (C) 2014 Elsevier Ltd. 保留所有权利。
Introduction: Shallow trophoblast invasion of the maternal spiral arteries contributes to impaired placental perfusion and is hypothesized to be involved in the pathophysiology of preeclampsia. Hypoxia is a potent stimulus for the release of adenosine.Methods: We investigated the effects of hypoxia and A(2B) adenosine receptor signaling on migration, invasion, proteolytic activity of matrix metalloproteinase (MMP)-2, expression of MMP-2 and vascular endothelial growth factor (VEGF) mRNA, and production of human chorionic gonadotropin (hCG) in trophoblast cells (HTR-8/SVneo, BeWo).Results: The adenosine A(2B) receptor agonist 5-N-ethylcarboxamidoadenosine (NECA) reduced trophoblast (HTR-8/SVneo and BeWo) migration at 2%, 8% and 21% O-2 compared to untreated control cells. A(2B) adenosine receptor stimulation decreased phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and stress-activated protein kinase/Jun-amino-terminal kinase (SAPK/JNK) at all three O-2 concentrations. ProMMP-2 activity, MMP-2 mRNA levels and hCG levels were markedly decreased after A(2B) adenosine receptor activation in trophoblast cells. Adenosine receptor A(2B) stimulation decreased VEGF expression at 2% and 8% O-2 but led to increased levels at 21% O-2.Conclusions: These data indicate A(2B) receptor activation blunts trophoblast migration possibly as a result of reduced activation of the MAPK signaling pathway and lower proMMP-2 levels. These data suggest a role for adenosine receptor An in placental development and possibly in the pathophysiology of preeclampsia. (C) 2014 Elsevier Ltd. All rights reserved.