Lysophosphatidic acid and sphingosine 1-phosphate stimulate endothelial cell wound healing

Am J Physiol Cell Physiol. 2000 Mar;278(3):C612-8. doi: 10.1152/ajpcell.2000.278.3.C612.


Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are potent lipid growth factors with similar abilities to stimulate cytoskeleton-based cellular functions. Their effects are mediated by a subfamily of G protein-coupled receptors (GPCRs) encoded by endothelial differentiation genes (edgs). We hypothesize that large quantities of LPA and S1P generated by activated platelets may influence endothelial cell functions. Using an in vitro wound healing assay, we observed that LPA and S1P stimulated closure of wounded monolayers of human umbilical vein endothelial cells and adult bovine aortic endothelial cells, which express LPA receptor Edg2, and S1P receptors Edg1 and Edg3. The two major components of wound healing, cell migration and proliferation, were stimulated individually by both lipids. LPA and S1P also stimulated intracellular Ca(2+) mobilization and mitogen-activated protein kinase (MAPK) phosphorylation. Pertussis toxin partially blocked the effects of both lipids on endothelial cell migration, MAPK phosphorylation, and Ca(2+) mobilization, implicating G(i)/(o)-coupled Edg receptor signaling in endothelial cells. LPA and S1P did not cross-desensitize each other in Ca(2+) responses, suggesting involvement of distinct receptors. Thus LPA and S1P affect endothelial cell functions through signaling pathways activated by distinct GPCRs and may contribute to the healing of wounded vasculatures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cattle
  • Cell Movement / drug effects
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • GTP-Binding Proteins / physiology
  • Humans
  • Kinetics
  • Lysophospholipids / pharmacology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Pertussis Toxin
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / physiology
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophospholipid
  • Signal Transduction / physiology
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Umbilical Veins
  • Virulence Factors, Bordetella / pharmacology
  • Wound Healing / drug effects*
  • Wound Healing / physiology


  • Lysophospholipids
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • Virulence Factors, Bordetella
  • sphingosine 1-phosphate
  • Pertussis Toxin
  • Mitogen-Activated Protein Kinases
  • GTP-Binding Proteins
  • Sphingosine
  • Calcium