Schlafen 5 调控内皮祖细胞修复血管内皮损伤的机制研究

Endothelial progenitor cells（EPCs ）are involved in repairing injured blood vessels, but the mechanism is still unknown and the therapeutic application is limited.Therefore, It is significant to study the function of EPCs in the prevention at early stages of the diseases induced by vascular injury. Previous study has indicated that Schlafen(Slfn) family is involved in regulating the function of EPCs. In our study, we found that Slfn5, a member of Slfn was a key regulator in EPCs proliferation. Further study showed that overexpression of Slfn5 significantly suppressed proliferation of EPCs. With these preliminary results, we hypothesize that Slfn5 affects the function of EPCs in the repair process after vascular injury. To explore the effect and mechanism of the proliferation, migration, adhesion and differentiation of EPCs induced by Slfn5 during vascular repair, we would study it by in vitro cell culture and establishment of carotid artery balloon injury model, using RNA interference, gene transfer, RNA Seq technology, etc. These findings will provide a new mechanism for modulating proliferation, migration, differentiation of EPCs. Slfn5 would be a new therapeutic target for vascular repair by EPCs ,which will provide a theoretical basis for clinical prevention of the diseases induced by vascular injury.

内皮祖细胞(EPCs)能促进血管损伤性疾病的内皮修复,但其机制尚不清楚，继而影响其临床应用的进展。因此，深入研究EPCs的内皮修复机制对防治血管损伤性疾病有重要临床价值。研究发现，细胞周期基因Schlafen（Slfn）家族与EPCs的血管修复能力有关。我们的前期研究显示，Slfn5在EPCs 表达，在EPCs增加Slfn5基因的表达，可抑制EPCs的增殖。据此，本项目提出Slfn5可能影响EPCs的内皮修复能力的假设。通过体外原代细胞培养及建立颈动脉球囊损伤模型，运用基因转染、RNA干扰、3-H掺入法、RNA测序等方法，研究Slfn5对EPCs增殖、迁移、粘附、分化的影响及对损伤血管内皮修复的作用，阐明Slfn5调节EPCs功能的机制，为临床防治血管损伤性疾病奠定理论基础，可望揭示Slfn5是介导EPCs治疗血管损伤性疾病的新靶点。

内皮祖细胞(EPCs)能促进血管损伤性疾病的内皮修复,但其机制尚不清楚，继而影响其临床应用的进展。因此，深入研究EPCs的内皮修复机制对防治血管损伤性疾病有重要临床价值。研究发现，细胞周期基因Schlafen（Slfn）家族与EPCs的血管修复能力有关。我们的前期研究显示，Slfn5在EPCs 表达，过表达Slfn5基因可抑制EPCs的增殖。因此，本研究在离体细胞水平观察Slfn5对EPCs增殖、粘附能力、迁移、血管环成形能力的影响，在动物实验水平研究Slfn5调控EPCs修复损伤血管内皮的作用，结果发现:在EPCs过表达Slfn 5基因，明显抑制EPCs的增殖、迁移、血管环形成能力，反之，在EPCs减弱Slfn 5基因的表达，明显促进EPCs的增殖、迁移、血管环形成能力。在在体颈动脉球囊损伤的动物模型上，移植过表达Slfn 5质粒的EPCs，结果发现在血管损伤后14天及21天，血管的再内皮化功能减弱，反之，移植干扰Slfn 5质粒的EPCs组，血管的再内皮化功能增强。以上结果表明，Slfn 5参与EPCs介导的血管损伤修复过程。为临床防治血管损伤性疾病奠定理论基础，可望揭示Slfn5是介导EPCs治疗血管损伤性疾病的新靶点。