Signalling mechanisms of SDF-induced endothelial cell proliferation and migration

Biochem Biophys Res Commun. 2005 Oct 7;335(4):1107-14. doi: 10.1016/j.bbrc.2005.08.006.

Abstract

The aim of our study was to investigate the effect of stromal-derived factor-1-alpha (SDF-1-alpha) on endothelial angiogenic effects. SDF-1-alpha (50 ng/ml) increased the number of cultured endothelial cells from 33,653 +/- 1183 to 55,398 +/- 2741, which significantly reduced by adding the BK(Ca)-inhibitor iberiotoxin, or the endothelial nitric oxide synthase-blocker, L-NMMA (n = 24, p < 0.05). Using the "Fences"-assay a significant increase of HUVEC migration induced by SDF-1-alpha was reported, which was blocked by the addition of iberiotoxin or L-NMMA (n = 12, p < 0.05). BK(Ca) open-state probability (NPo) was analysed using the patch-clamp technique and NPo was increased from 0.003 (control) to 0.052 (SDF-1-alpha; n = 10, p < 0.05). NO synthesis was measured using a cGMP-radioimmunoassay. A significant increase of cGMP levels from 0.952 pmol/mg protein to 2.179 pmol/mg protein was observed, that was abolished by L-NMMA and significantly reduced by iberiotoxin (n=15, p<0.05). SDF-1-alpha increases endothelial proliferation and migration involving the activation of BK(Ca) and an increased production of NO.

MeSH terms

  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC / pharmacology*
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology*
  • Humans
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Large-Conductance Calcium-Activated Potassium Channels
  • Nitric Oxide / metabolism*
  • Potassium Channels, Calcium-Activated / drug effects
  • Potassium Channels, Calcium-Activated / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Nitric Oxide