Hypoxia enhances FGF2- and VEGF-stimulated human placental artery endothelial cell proliferation: roles of MEK1/2/ERK1/2 and PI3K/AKT1 pathways.
Hypoxia enhances FGF2- and VEGF-stimulated human placental artery endothelial cell proliferation: roles of MEK1/2/ERK1/2 and PI3K/AKT1 pathways.
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DOI：
10.1016/j.placenta.2009.10.007
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发表时间：
2009-12
期刊：
影响因子：
3.8
通讯作者：
Zheng, J.
中科院分区：
文献类型：
--
作者：
Wang, K.;Jiang, Y-z.;Chen, D-b.;Zheng, J.
胎盘发育发生在低氧（2 - 8%O2）环境下，这对胎盘发育和血管生成至关重要。在本研究中，我们在人胎盘动脉内皮细胞中检测了缺氧是否通过丝裂原活化蛋白激酶激酶1/2（MEK 1/2）/细胞外信号调节激酶1/2（ERK 1/2）和磷脂酰肌醇-3激酶（PI3K）/v-akt鼠胸腺瘤病毒癌基因同源物（AKT1）途径影响成纤维细胞生长因子2（FGF 2）和血管内皮生长因子（VEGF）刺激的细胞增殖。HPAE）细胞。我们观察到，在常氧（~20%O2）下，FGF2和VEGF剂量依赖性地刺激细胞增殖。低氧（3%O2）显着促进FGF 2和VEGF刺激的细胞增殖相比，常氧。在常氧和缺氧条件下，FGF2迅速诱导ERK 1/2和AKT 1磷酸化，而VEGF诱导ERK 1/2磷酸化，但不诱导AKT 1磷酸化。然而，与常氧相比，缺氧并没有显著改变FGF 2和VEGF诱导的ERK 1/2和AKT 1磷酸化。20 μ M的PD98059（一种MEK 1/2抑制剂）和5 μ M的LY294002（一种PI3K抑制剂）分别减弱FGF 2和VEGF诱导的ERK 1/2和AKT 1磷酸化。PD98059即使在显著抑制FGF 2诱导的ERK 1/2磷酸化（20 μ M）和导致细胞损失（40 μ M）的剂量下，也不影响FGF 2刺激的细胞增殖，这一点已由U0126（另一种有效的MEK 1/2抑制剂）证实。然而，PD98059剂量依赖性地抑制VEGF刺激的细胞增殖。相反，LY294002剂量依赖性地抑制FGF 2刺激的细胞增殖，但不抑制VEGF刺激的细胞增殖。这些数据表明，在MEK 1/2/ERK 1/2和PI3K/AKT 1途径差异介导FGF 2和VEGF刺激的HPAE细胞增殖。这些结果还表明，缺氧促进FGF 2和VEGF刺激的细胞增殖，而不分别进一步激活PI3K/AKT 1和MEK 1/2/ERK 1/2。
Placental development occurs under a low oxygen (2–8% O2) environment, which is critical for placental development and angiogenesis. In this study, we examined if hypoxia affected fibroblast growth factor 2 (FGF2)- and vascular endothelial growth factor (VEGF)-stimulated cell proliferation via the mitogen-activated protein kinase kinase 1/2 (MEK1/2)/extracellular signal-regulated kinases 1/2 (ERK1/2) and phosphatidylinositol-3 kinase (PI3K)/v-akt murine thymomaviral oncogene homologue (AKT1) pathways in human placental artery endothelial (HPAE) cells. We observed that under normoxia (~20% O2), FGF2 and VEGF dose-dependently stimulated cell proliferation. Hypoxia (3% O2) significantly promoted FGF2- and VEGF-stimulated cell proliferation as compared to normoxia. Under both normoxia and hypoxia, FGF2 rapidly induced ERK1/2 and AKT1 phosphorylation, while VEGF induced ERK1/2, but not AKT1 phosphorylation. However, hypoxia did not significantly alter FGF2- and VEGF-induced ERK1/2 and AKT1 phosphorylation as compared to normoxia. PD98059 (a MEK1/2 inhibitor) at 20 μM and LY294002 (a PI3K inhibitor) at 5 μM attenuated FGF2- and VEGF-induced phosphorylation of ERK1/2 and AKT1, respectively. PD98059, even at doses that drastically inhibited FGF2-induced ERK1/2 phosphorylation (20 μM) and caused cell loss (40 μM), did not affect FGF2-stimulated cell proliferation, which was confirmed by U0126 (another potent MEK1/2 inhibitor). PD98059, however, dose-dependently inhibited VEGF-stimulated cell proliferation. Conversely, LY294002 dose-dependently inhibited FGF2-, but not VEGF-stimulated cell proliferation. These data suggest that in the MEK1/2/ERK1/2 and PI3K/AKT1 pathways differentially mediate FGF2- and VEGF-stimulated HPAE cell proliferation. These results also indicate that hypoxia promotes FGF2- and VEGF-stimulated cell proliferation without further activation of the PI3K/AKT1 and MEK1/2/ERK1/2, respectively.
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影响因子：
4.8
作者：
Das, M;Bouchey, DM;Stenmark, KR
通讯作者：
Stenmark, KR
DOI：
10.1159/000301658
发表时间：
1974-01-01
期刊：
GYNECOLOGIC INVESTIGATION
影响因子：
--
作者：
ROSENFELD, CR;MORRISS, FH;BATTAGLIA, FC
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影响因子：
6
作者：
Jauniaux, E;Watson, AL;Burton, GJ
通讯作者：
Burton, GJ
DOI：
10.1165/ajrcmb.23.5.3921
发表时间：
2000-11-01
影响因子：
6.4
作者：
Jin, NJ;Hatton, N;Rhoades, RA
通讯作者：
Rhoades, RA
影响因子：
3.8
作者：
Mata-Greenwood, Eugenia;Liao, Wu-Xiang;Chen, Dong-Bao
通讯作者：
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