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Sphingosine-1-phosphate induces VEGF-C expression through a MMP-2/FGF-1/FGFR-1-dependent pathway in endothelial cells in vitro
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Sphingosine-1-phosphate induces VEGF-C expression through a MMP-2/FGF-1/FGFR-1-dependent pathway in endothelial cells in vitro
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Sphingosine-1-phosphate induces VEGF-C expression through a MMP-2/FGF-1/FGFR-1-dependent pathway in endothelial cells in vitro
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Journal Article
Sphingosine-1-phosphate induces VEGF-C expression through a MMP-2/FGF-1/FGFR-1-dependent pathway in endothelial cells in vitro
2013
Overview
Aim:
To investigate whether sphingosine-1-phosphate (S1P), a potent angiogenic factor, induced vascular endothelial growth factor-C (VEGF-C) expression in endothelial cells
in vitro
and to examine its underlying mechanisms.
Methods:
Human umbilical vein endothelial cells (HUVECs) were examined. VEGF-C mRNA expression in the cells was assessed using real-time PCR. VEGF-C protein and FGFR-1 phosphorylation in the cells were measured with ELISA. RNA interference was used to downregulate the expression of matrix metalloproteinase-2 (MMP-2), fibroblast growth factor-1 (FGF-1) and FGF receptor-1 (FGFR-1).
Results:
Incubation of HUVECs with S1P (1, 5, and 10 μmol/L) significantly increased VEGF-C expression. The effect was blocked by pretreatment with the MMP inhibitor GM6001 or the FGFR inhibitor SU5402, but not the EGFR inhibitor AG1478. The effect was also blocked in HUVECs that were transfected with FGFR-1 or MMP-2 siRNA. Furthermore, incubation of HUVECs with S1P (5 μmol/L) significantly increased FGFR-1 phosphorylation, which was blocked by GM6001. Moreover, knockdown of FGF-1, not FGF-2, in HUVECs with siRNAs, blocked S1P-induced VEGF-C expression.
Conclusion:
S1P induces VEGF-C expression through a MMP-2/ FGF-1/FGFR-1-dependent pathway in HUVECs.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Enzyme-Linked Immunosorbent Assay
/ Fibroblast Growth Factor 1 - genetics
/ Fibroblast Growth Factor 1 - metabolism
/ Human Umbilical Vein Endothelial Cells
/ Humans
/ Lysophospholipids - pharmacology
/ Lysophospholipids - physiology
/ Matrix Metalloproteinase 2 - genetics
/ Matrix Metalloproteinase 2 - metabolism
/ Original
/ Real-Time Polymerase Chain Reaction
/ Receptor, Fibroblast Growth Factor, Type 1 - genetics
/ Receptor, Fibroblast Growth Factor, Type 1 - metabolism
/ RNA, Small Interfering - genetics
/ RNA, Small Interfering - pharmacology
/ Signal Transduction - drug effects
/ Sphingosine - analogs & derivatives
/ Vaccine
