Schlafen 1 Inhibits the Proliferation and Tube Formation of Endothelial Progenitor Cells

Endothelial progenitor cells (EPCs) are the major source of cells that restore the endothelium during reendothelialization. This study was designed to investigate whether Schlafen 1 (Slfn1) has an effect on the proliferation and tube formation of EPCs in vivo. Slfn1 was expressed in rat EPCs. The overexpression of Slfn1 suppressed the proliferation and tube formation of EPCs; conversely, the knockdown of Slfn1 by shRNA promoted the proliferation and tube formation of EPCs. Furthermore, when Slfn1 was overexpressed, the EPCs were arrested in the G1 phase of the cell cycle. In contrast, when Slfn1 was knocked down, the EPCs progressed into the S phase of the cell cycle. Additionally, the overexpression of Slfn1 decreased the expression of Cyclin D1, whereas the knockdown of Slfn1 increased the expression of Cyclin D1; these findings suggest that Cyclin D1 is downstream of Slfn1 in Slfn1-mediated EPC proliferation. Taken together, these results indicate a key role for Slfn1 in the regulation of EPC biological behavior, which may provide a new target for the use of EPCs during reendothelialization.

内皮祖细胞（Endothelial progenitor cells, EPCs）是再内皮化（reendothelialization）过程中修复内皮的主要细胞来源。本研究旨在探讨Schlafen 1（Slfn1）是否在体内对EPC的增殖与管形成功能具有调控作用。研究发现，Slfn1在大鼠EPC中存在表达。过表达Slfn1可抑制EPC的增殖与管形成能力；反之，通过短发夹RNA（short hairpin RNA, shRNA）敲低Slfn1则可促进EPC的增殖与管形成。进一步研究显示，过表达Slfn1会使EPC阻滞于细胞周期的G1期；与之相反，敲低Slfn1可促使EPC进入细胞周期S期。此外，过表达Slfn1会降低细胞周期蛋白D1（Cyclin D1）的表达水平，而敲低Slfn1则可上调Cyclin D1的表达，上述结果提示Cyclin D1是Slfn1介导的EPC增殖通路中的下游靶分子。综上，本研究结果表明Slfn1在调控EPC的生物学行为中发挥关键作用，可为再内皮化过程中EPC的应用提供全新靶点。