Direct and differential effects of stem cell factor on the neovascularization activity of endothelial progenitor cells

被引:36
作者
Kim, Koung Li [1 ,2 ]
Meng, Yongsun [2 ]
Kim, Ji Yeon [1 ]
Baek, Eun Jung [3 ]
Suh, Wonhee [1 ,2 ]
机构
[1] Ajou Univ, Coll Pharm, Suwon 443749, South Korea
[2] CHA Univ, Coll Life Sci, Dept Biomed Sci, Pochon Si 487010, Gyeonggi Do, South Korea
[3] Hanyang Univ, Coll Med, Dept Lab Med, Guri Si 471701, Gyeonggi Do, South Korea
基金
新加坡国家研究基金会;
关键词
c-Kit; Endothelial progenitor cells; Neovascularization; Stem cell factor; C-KIT EXPRESSION; HEMATOPOIETIC-CELLS; BONE-MARROW; FACTOR SCF; VASCULOGENESIS; RECEPTOR;
D O I
10.1093/cvr/cvr161
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims 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. Methods and 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. Conclusion 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.
引用
收藏
页码:132 / 140
页数:9
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