Caveolin-1 orchestrates fibroblast growth factor 2 signaling control of angiogenesis in placental artery endothelial cell caveolae

Autor: Jing Zheng, Dong-bao Chen, Wen Wang, Quan Luo, Lin Feng, Hong-hai Zhang, Wu-Xiang Liao
Rok vydání: 2012
Předmět:
Time Factors
Physiology
Angiogenesis
Placenta
Caveolin 1
Clinical Biochemistry
Neovascularization
Physiologic
Angiogenesis Inhibitors
Biology
Caveolae
Transfection
Fibroblast growth factor
Article
Cell Movement
Pregnancy
Animals
Humans
Receptor
Fibroblast Growth Factor
Type 1
Phosphorylation
Protein Kinase Inhibitors
Cells
Cultured
PI3K/AKT/mTOR pathway
Cell Proliferation
Phosphoinositide-3 Kinase Inhibitors
Mitogen-Activated Protein Kinase 1
Tube formation
Mitogen-Activated Protein Kinase 3
Sheep
integumentary system
Fibroblast growth factor receptor 1
Endothelial Cells
Cell Differentiation
Arteries
Cell Biology
Molecular biology
Cell biology
Endothelial stem cell
embryonic structures
Tyrosine
Female
Fibroblast Growth Factor 2
RNA Interference
Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-akt
Protein Binding
Signal Transduction
Zdroj: Journal of Cellular Physiology. 227:2480-2491
ISSN: 0021-9541
DOI: 10.1002/jcp.22984
Popis: 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.
Databáze: OpenAIRE
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