Caveolin-1 orchestrates fibroblast growth factor 2 signaling control of angiogenesis in placental artery endothelial cell caveolae.
Caveolin-1 orchestrates fibroblast growth factor 2 signaling control of angiogenesis in placental artery endothelial cell caveolae.
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DOI：
10.1002/jcp.22984
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发表时间：
2012-06
影响因子：
5.6
通讯作者：
Chen, Dong-Bao
中科院分区：
文献类型：
--
作者：
Feng, Lin;Liao, Wu-Xiang;Luo, Quan;Zhang, Hong-Hai;Wang, Wen;Zheng, Jing;Chen, Dong-Bao
成纤维细胞生长因子（FGF）受体1（FGFR 1）蛋白在离体和体外的羊胎儿胎盘动脉中以长、短和部分截短形式表达。在FGF 2刺激后，绵羊胎儿胎盘动脉内皮细胞（oFPAE）中长和短FGFR 1均被酪氨酸磷酸化，PI 3 K/AKT 1和ERK 1/2通路以浓度和时间依赖性方式被激活。阻断PI 3 K/AKT 1通路减弱了FGF 2刺激的细胞增殖和迁移以及管形成;阻断ERK 1/2通路废除了FGF 2刺激的管形成，部分抑制了细胞增殖，但不改变细胞迁移。AKT 1和ERK 1/2均与小窝蛋白-1共分级分离，并在小窝中被FGF 2激活。甲基-β-环糊精破坏小窝可抑制FGF 2激活AKT 1和ERK 1/2。FGFR 1在小窝中发现，在那里它与小窝蛋白-1物理结合。FGF 2刺激FGFR 1从小窝蛋白-1解离。下调caveolin-1可显着减弱FGF 2诱导的AKT 1和ERK 1/2激活，并抑制FGF 2诱导的oFCAE细胞增殖、迁移和管形成。用小窝蛋白-1支架结构域肽预处理以模拟小窝蛋白-1过表达也抑制了这些FGF 2诱导的血管生成反应。这些数据表明，小窝作为一个平台，通过时空区室化FGFR 1和AKT 1和ERK 1/2信号传导模块调节FGF 2诱导的血管生成;主要的小窝结构蛋白小窝蛋白-1与FGFR 1相互作用，矛盾地调节FGF 2诱导的PI 3 K/AKT 1和ERK 1/2途径的激活，协调调节胎盘血管生成。
Fibroblast growth factor (FGF) receptor 1 (FGFR1) protein was expressed as the long and short as well as some truncated forms in ovine fetoplacental artery ex vivo and in vitro. Upon FGF2 stimulation, both the long and short FGFR1s were tyrosine phosphorylated and the PI3K/AKT1 and ERK1/2 pathways were activated in a concentration- and time- dependent manner in ovine fetoplacental artery endothelial (oFPAE) cells. Blockade of the PI3K/AKT1 pathway attenuated FGF2-stimulated cell proliferation and migration as well as tube formation; blockade of the ERK1/2 pathway abolished FGF2-stimulated tube formation and partially inhibited cell proliferation and did not alter cell migration. Both AKT1 and ERK1/2 were co-fractionated with caveolin-1 and activated by FGF2 in the caveolae. Disruption of caveolae by methyl-β-cyclodextrin inhibited FGF2 activation of AKT1 and ERK1/2. FGFR1 was found in the caveolae where it physically binds to caveolin-1. FGF2 stimulated dissociation of FGFR1 from caveolin-1. Downregulation of caveolin-1 significantly attenuated the FGF2-induced activation of AKT1 and ERK1/2 and inhibited FGF2-induced cell proliferation, migration and tube formation in oFPAE cells. Pretreatment with a caveolin-1 scaffolding domain peptide to mimic caveolin-1 overexpression also inhibited these FGF2-induced angiogenic responses. These data demonstrate that caveolae function as a platform for regulating FGF2-induced angiogenesis through spatiotemporally compartmentalizing FGFR1 and the AKT1 and ERK1/2 signaling modules; the major caveolar structural protein caveolin-1 interacts with FGFR1 and paradoxically regulates FGF2-induced activation of PI3K/AKT1 and ERK1/2 pathways that coordinately regulate placental angiogenesis.
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DOI：
10.1073/pnas.88.17.7625
发表时间：
1991-09-01
影响因子：
11.1
作者：
BERNARD, O;LI, M;REID, HH
通讯作者：
REID, HH
影响因子：
3.8
作者：
Cooke, Flavia N. T.;Pennington, Kathleen A.;Ealy, Alan D.
通讯作者：
Ealy, Alan D.
影响因子：
3.8
作者：
Arany, E;Hill, DJ
通讯作者：
Hill, DJ
影响因子：
4.8
作者：
Liu, J;Wang, XB;Lisanti, MP
通讯作者：
Lisanti, MP
DOI：
10.1161/01.atv.0000070546.16946.3a
发表时间：
2003-07-01
影响因子：
8.7
作者：
Frank, PG;Woodman, SE;Lisanti, MP
通讯作者：
Lisanti, MP