Sphingosine-1-phosphate induces VEGF-C expression through a MMP-2/FGF-1/FGFR-1-dependent pathway in endothelial cells in vitro

Chi Hao Chang, Yuan Lin Huang, Ming Kwang Shyu, Shee Uan Chen, Chih Hsin Lin, Tsai Kai Ju, Jenher Lu, Hsinyu Lee

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)360-366
Number of pages7
JournalActa Pharmacologica Sinica
Volume34
Issue number3
DOIs
Publication statusPublished - Mar 2013
Externally publishedYes

Keywords

  • fibroblast growth factor receptor-1
  • fibroblast growth factor-1
  • GM6001
  • human umbilical vein endothelial cells
  • matrix metalloproteinase-2
  • RNA interference
  • sphingosine-1-phosphate
  • SU5402
  • transactivation
  • VEGF-C

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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