Differential activation of multiple signalling pathways dictates eNOS Upregulation by FGF2 but not VEGF in placental artery endothelial cells
Differential activation of multiple signalling pathways dictates eNOS Upregulation by FGF2 but not VEGF in placental artery endothelial cells
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DOI：
10.1016/j.placenta.2008.05.005
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发表时间：
2008-08-01
期刊：
影响因子：
3.8
通讯作者：
Chen, Dong-Bao
中科院分区：
文献类型：
--
作者：
Mata-Greenwood, Eugenia;Liao, Wu-Xiang;Chen, Dong-Bao
成纤维细胞生长因子（FGF2）。但血管内皮生长因子 (VEGF) 不上调内皮一氧化氮合酶 (eNOS) 蛋白表达。至少部分是通过激活绵羊胎儿胎盘动脉内皮 (oFPAE) 细胞中的细胞外信号调节激酶 2/1 (ERK2/1)。在此，我们进一步研究了 FGF2 和 VEGF 对其他信号通路的时间影响，包括丝裂原激活蛋白激酶 (MAPK) 的成员（Jun N 末端激酶 JNK 1/2 和 p38MAPK）。磷脂酰肌醇-3 激酶/v-akt 鼠胸腺瘤病毒癌基因同源物 I (PI3K/AKTI) 和酪氨酸激酶 c-SRC。并检查这些途径中的一个或多个是否在 FGF2 和 VEGF 对 eNOS 的差异调节中发挥作用。我们首先在 oFPAE 细胞中证实了这一点。 FGF2，但不是 VEGF。 eNOS 蛋白增加。 FGF2 以时间和浓度依赖性方式刺激 eNOS 蛋白，这也取决于油细胞密度。 FGF2 引发持续（5 分钟至 12 小时），而 VEGF 仅刺激短暂（5 分钟）ERK2/1 磷酸化。 FGF2 刺激 ERK2/I 磷酸化的能力是 VEGF 的 1.7 倍。 FGF2和VEGF仅在5分钟内短暂激活JNK1/2和AKT1：然而，FGF2的刺激作用比VEGF更强。 FGF-2和VEGF在5分钟时没有显着激活p38MAPK，然而，VEGF在60分钟时刺激p38MAPK磷酸化。 VEGF 但不是 FGF2 显着刺激 c-SRC 磷酸化。 MEK-ERK2/1 (PD98059) 抑制剂。 JNK1/2 (SP600125) 和 PI3K (wortmannin)，但不是 p38MAPK (SB203580) 和 SRC (PP2)，降低了 FGF2 增加的 eNOS 蛋白表达。因此，FGF2诱导的eNOS蛋白表达需要激活多种信号传导途径，包括ERK2/1、JNK1/2和PI3K/AKT1。 FGF2 和 VEGF 激活这些途径的强度和时间模式的差异可能解释了它们对 OFPAE 细胞中 eNOS 表达的不同影响。由爱思唯尔有限公司出版
Fibroblast growth factor (FGF2). but not vascular endothelial growth factor (VEGF), upregulates endothelial nitric oxide synthase (eNOS) protein expression. at least partially, via activation of extracellular signal-regulated kinase 2/1 (ERK2/1) in ovine fetoplacental artery endothelial (oFPAE) cells. Herein we further investigated the temporal effects of FGF2 and VEGF oil other signalling pathways including members (Jun N-terminal kinase JNK 1/2 and p38MAPK) of mitogen-activated protein kinases, (MAPK). phosphatidylinositol-3 kinase/v-akt murine thymoma viral oncogene homologue I (PI3K/AKTI), and the tyrosine kinase c-SRC. and examined if either one or more of these pathways play a role in file differential regulation of eNOS by FGF2 and VEGF. We first confirmed that in oFPAE cells. FGF2, but not VEGF. increased eNOS protein. FGF2 stimulated eNOS protein in a time- and concentration-dependent manner, which also depended oil cell density. FGF2 provoked Sustained (5 min to 12 h) whereas VEGF only stimulated transient (5 min) ERK2/1 phosphorylation. FGF2 was 1.7-fold more potent ill stimulating ERK2/ I phosphorylation than VEGF. FGF2 and VEGF only transiently activated JNK1/2 and AKT1 within 5 min: however, FGF2 was it stronger stimulus than VEGF. FGF-2 and VEGF did not significantly activate p38MAPK at 5 min, however, VEGF stimulated p38MAPK phosphorylation at 60 min. VEGF but not FGF2 significantly stimulated c-SRC phosphorylation. Inhibitors of MEK-ERK2/1 (PD98059). JNK1/2 (SP600125) and PI3K (wortmannin), but not p38MAPK (SB203580) and SRC (PP2), decreased the FGF2-increased eNOS protein expression. Thus, the FGF2-induced eNOS protein expression requires activation Of Multiple Signalling pathways including ERK2/1, JNK1/2 and PI3K/AKT1. Differences in intensity and temporal patterns of activation of these pathways by FGF2 and VEGF may account for their differential effects oil eNOS expression in OFPAE cells. Published by Elsevier Ltd.