Signalling mechanisms of SDF-induced endothelial cell proliferation and migration

• Published in: Biochemical and biophysical research communications 2005-10, Vol.335 (4), p.1107-1114
• Main Authors: Kuhlmann, Christoph Rüdiger Wolfram, Schaefer, Christian Alexander, Reinhold, Lars, Tillmanns, Harald, Erdogan, Ali
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Cell Movement - drug effects; Cell Movement - physiology; CELL PROLIFERATION; Cell Proliferation - drug effects; Cells, Cultured; Chemokine CXCL12; Chemokines, CXC - pharmacology; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - physiology; Humans; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; K + channels; Large-Conductance Calcium-Activated Potassium Channels; Migration; NITRIC OXIDE; Nitric Oxide - metabolism; Potassium Channels, Calcium-Activated - drug effects; Potassium Channels, Calcium-Activated - metabolism; Proliferation; PROTEINS; RADIOIMMUNOASSAY; SDF-1-α; Signal Transduction - drug effects; Signal Transduction - physiology; SYNTHESIS
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.08.006

The aim of our study was to investigate the effect of stromal-derived factor-1-α (SDF-1-α) on endothelial angiogenic effects. SDF-1-α (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-α 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-α; 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-α increases endothelial proliferation and migration involving the activation of BK Ca and an increased production of NO.