Stromal Cell-Derived Factor-1α Promotes Endothelial Colony-Forming Cell Migration Through the Ca2+-Dependent Activation of the Extracellular Signal-Regulated Kinase 1/2 and Phosphoinositide 3-Kinase/AKT Pathways.

摘要: Stromal cell-derived factor-1α (SDF-1α) drives endothelial colony-forming cell (ECFC) homing and incorporation within neovessels, thereby restoring tissue perfusion in ischemic tissues favoring tumor vascularization metastasis. SDF-1α stimulates ECFC migration by activating the Gi-protein-coupled receptor, CXCR4, then engaging phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Sporadic evidence showed that may also act through an increase intracellular Ca2+ concentration ([Ca2+]i) bone marrow-derived hematopoietic progenitor cells fully differentiated cells. Of note, recent demonstrated signals play a key role controlling proangiogenic activity of ECFCs. The present investigation was, therefore, undertaken to assess whether how induces motility triggering signals. We found caused dose-dependent [Ca2+]i was inhibited ADM3100, selective CXCR4 antagonist. Pharmacological manipulation revealed response shaped initial release inositol-1,4,5-trisphosphate receptors (InsP3Rs), followed sustained phase extracellular entry store-operated channels. InsP3-dependent (SOCE) were both necessary for SDF-1α-induced signal-regulated kinases 1/2 (ERK 1/2) AKT phosphorylation. Finally, employed signals, ERK 1/2, PI3K/AKT promote vitro neovessel formation vivo. These data, provide first Ca2+-dependent activation pathways.