title: Direct and differential effects of stem cell factor on the neovascularization activity of endothelial progenitor cells.
abstract: OBJECTIVE
  Previous studies on the role of stem cell factor (SCF) in endothelial progenitor cell (EPC)-mediated neovascularization have focused on the EPC mobilization and homing process. However, the direct effects of SCF on neovascularization activity of EPCs have not been characterized. We sought to determine whether SCF regulates the neovascularization ability of EPCs by comparing its roles in mature endothelial cells.
  
  
  RESULTS
  In vitro and in vivo assays revealed that SCF substantially increased the neovascularization activity of human EPCs through the c-Kit receptor. Notably, the SCF-induced increase in neovascularization activity was substantially greater in EPCs than that in human umbilical vein endothelial cells (HUVECs). SCF-induced phosphorylation of c-Kit and downstream signalling molecules was consistently found to be more potent and longer-lasting in EPCs than in HUVECs. This high responsiveness of EPCs to SCF was explained by the finding that the cell-surface expression of c-Kit is far higher in EPCs than in HUVECs. A c-Kit promoter assay revealed that the increased expression of c-Kit in EPCs could be attributed to the greater expression of stem cell leukaemia, LIM-only 2, and GATA-binding protein 2.
  
  
  CONCLUSIONS
  In addition to its documented role in the mobilization and recruitment of EPCs, our findings show that SCF directly enhances the neovascularization activity of EPCs. Furthermore, the present study provides further evidence that EPCs exhibit differentially greater responsiveness to hypoxia-inducible cytokines, including SCF, than mature endothelial cells, suggesting that EPCs in ischaemic tissues function differently from mature endothelial cells, although they exhibit very similar phenotypes.
authors.affiliation: College of Pharmacy, Ajou University, San 5, Woncheon-Dong, Yeongtong-Gu, Suwon 443-749, Korea.
authors.forename: Koung Li
authors.initials: KL
authors.lastname: Kim
authors.forename: Yongsun
authors.initials: Y
authors.lastname: Meng
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Baek
authors.forename: Wonhee
authors.initials: W
authors.lastname: Suh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis; D042783:Endothelial Cells / Q000166:cytology*; D050989:GATA2 Transcription Factor; D006801:Humans; D060588:LIM Domain Proteins / Q000032:analysis; D018919:Neovascularization, Physiologic; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000502:physiology; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D050989:GATA2 Transcription Factor; D060588:LIM Domain Proteins; D011518:Proto-Oncogene Proteins; D019009:Proto-Oncogene Proteins c-kit; D019089:Stem Cell Factor; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C494711:GATA2 protein, human; C085117:LMO2 protein, human; C067143:TAL1 protein, human