Zheng Hao, Fu Guosheng, Dai Tao, Huang He
Department of Cardiovascular Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, PR China.
J Cardiovasc Pharmacol. 2007 Sep;50(3):274-80. doi: 10.1097/FJC.0b013e318093ec8f.
Stromal cell-derived factor (SDF)-1alpha, a member of the chemokine CXC subfamily, plays an important role in regulation of a variety of cellular functions of endothelial progenitor cells such as cell migration, proliferation, survival and angiogenesis. However, there is relatively little information linking the cellular functions and individual signaling pathways mediated by SDF-1alpha in endothelial progenitor cells. In our study, we showed that endothelial progenitor cells expressed CXCR4 by reverse transcription polymerase chain reaction and flow cytometric analysis. Functional analysis showed that SDF-1alpha induced a concentration-dependent migration of endothelial progenitor cells and the migration was CXCR4 dependent as confirmed by the total inhibition by AMD3100, a CXCR4-specific peptide antagonist. The migration can also be nearly completely blocked by phosphoinositide 3-kinase inhibitors (LY294002 and wortmannin) and eNOS inhibitor (N-nitro-arginine methyl ester), whereas mitogen-activated protein kinase/ERK inhibitor (PD98059) had no significant effect on SDF-1alpha-induced migration. The treatment of endothelial progenitor cells with SDF-1alpha resulted in time and concentration-dependent Akt, eNOS, and ERK1/2 phosphorylation. These findings suggested that phosphoinositide 3-kinase/Akt/eNOS, but not mitogen-activated protein kinase/ERK, signal transduction pathway may be involved in SDF-1alpha mediated migration of endothelial progenitor cells.
基质细胞衍生因子（SDF）-1α是趋化因子CXC亚家族的成员之一，在调节内皮祖细胞的多种细胞功能（如细胞迁移、增殖、存活和血管生成）中发挥重要作用。然而，关于SDF-1α在内皮祖细胞中介导的细胞功能与单个信号通路之间的联系，相关信息相对较少。在我们的研究中，通过逆转录聚合酶链反应和流式细胞术分析表明内皮祖细胞表达CXCR4。功能分析显示，SDF-1α诱导内皮祖细胞呈浓度依赖性迁移，并且如CXCR4特异性肽拮抗剂AMD3100完全抑制所证实，该迁移是CXCR4依赖性的。迁移也可被磷酸肌醇3激酶抑制剂（LY294002和渥曼青霉素）和eNOS抑制剂（N-硝基-精氨酸甲酯）几乎完全阻断，而丝裂原活化蛋白激酶/ERK抑制剂（PD98059）对SDF-1α诱导的迁移没有显著影响。用SDF-1α处理内皮祖细胞导致Akt、eNOS和ERK1/2磷酸化呈时间和浓度依赖性。这些发现表明，磷酸肌醇3激酶/Akt/eNOS信号转导通路而非丝裂原活化蛋白激酶/ERK信号转导通路可能参与SDF-1α介导的内皮祖细胞迁移。
