Sphingosine 1-phosphate induces angiogenesis

Its angiogenic action and signaling mechanism in human umbilical vein endothelial cells

Ok Hee Lee, Young Mi Kim, You Mie Lee, Eun Joung Moon, Doo Jae Lee, Jae Hong Kim, Kyu Won Kim, Young-Guen Kwon

Research output: Contribution to journalArticle

312 Citations (Scopus)

Abstract

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite abundantly stored in platelets and released upon platelet activation. Recently, S1P has been postulated for its potential roles in angiogenesis. In this study, we provided several lines of evidence showing that S1P has angiogenic activity. In vitro, S1P stimulated DNA synthesis and chemotactic motility of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, reaching a near maximum at 1 μM. S1P also significantly induced tube formation of HUVECs on Matrigel. Matrigel plug assay in mice revealed that S1P promotes angiogenesis in vivo. In addition, exposure of HUVECs to S1P led to rapid activation of extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein kinase (p38 MAPK) in a pertussis toxin (PTX)-sensitive manner. Notably, HUVEC migration and tube formation in response to S1P were completely blocked by pretreatment with PTX. Further, the MEK inhibitor U0126 markedly inhibited S1P-induced tube formation but S1P-induced migration was not affected by inhibition of ERK and p38 MAPK. Taken together, these results indicate that S1P induces angiogenesis predominantly via G(i) protein-coupled receptors in endothelial cells and suggest that S1P may act as an important modulator of platelet-induced angiogenesis.

Original languageEnglish
Pages (from-to)743-750
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume264
Issue number3
DOIs
Publication statusPublished - 1999 Nov 2

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Endothelial cells
Human Umbilical Vein Endothelial Cells
Platelets
Extracellular Signal-Regulated MAP Kinases
Pertussis Toxin
p38 Mitogen-Activated Protein Kinases
sphingosine 1-phosphate
Blood Platelets
Chemical activation
Sphingolipids
Mitogen-Activated Protein Kinase Kinases
Platelet Activation
Metabolites
G-Protein-Coupled Receptors
Modulators
Cell Movement
Assays
Endothelial Cells

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, Ok Hee ; Kim, Young Mi ; Lee, You Mie ; Moon, Eun Joung ; Lee, Doo Jae ; Kim, Jae Hong ; Kim, Kyu Won ; Kwon, Young-Guen. / Sphingosine 1-phosphate induces angiogenesis : Its angiogenic action and signaling mechanism in human umbilical vein endothelial cells. In: Biochemical and Biophysical Research Communications. 1999 ; Vol. 264, No. 3. pp. 743-750.
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Sphingosine 1-phosphate induces angiogenesis : Its angiogenic action and signaling mechanism in human umbilical vein endothelial cells. / Lee, Ok Hee; Kim, Young Mi; Lee, You Mie; Moon, Eun Joung; Lee, Doo Jae; Kim, Jae Hong; Kim, Kyu Won; Kwon, Young-Guen.

In: Biochemical and Biophysical Research Communications, Vol. 264, No. 3, 02.11.1999, p. 743-750.

Research output: Contribution to journalArticle

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AU - Lee, Ok Hee

AU - Kim, Young Mi

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