Preconditioning before bone marrow transplantation such as irradiation causes vascular endothelial cells damage and promoting the repair of damaged endothelial cells is beneficial for hematopoietic reconstitution. Pigment epithelium-derived factor (PEDF) regulates vascular permeability. However, PEDF’s role in the repair of damaged endothelial cells during preconditioning remains unclear. The purpose of our study is to investigate PEDF’s effect on preconditioning-induced damage of endothelial cells and hematopoietic reconstitution. Damaged endothelial cells induced by irradiation was co-cultured with hematopoietic stem cells (HSC) in the absence or presence of PEDF followed by analysis of HSC number, cell cycle, colony formation and differentiation. In addition, PEDF was injected into mice model of bone marrow transplantation followed by analysis of bone marrow injury, HSC number and peripheral hematopoietic reconstitution as well as the secretion of cytokines (SCF, TGF-β, IL-6 and TNF-α). Comparisons between two groups were performed by student t-test and multiple groups by one-way or two-way ANOVA. Damaged endothelial cells reduced HSC expansion and colony formation, induced HSC cell cycle arrest and apoptosis and promoted HSC differentiation as well as decreased PEDF expression. Addition of PEDF increased CD144 expression in damaged endothelial cells and inhibited the increase of endothelial permeability, which were abolished after addition of PEDF receptor inhibitor Atglistatin. Additionally, PEDF ameliorated the inhibitory effect of damaged endothelial cells on HSC expansion in vitro. Finally, PEDF accelerated hematopoietic reconstitution after bone marrow transplantation in mice and promoted the secretion of SCF, TGF-β and IL-6. PEDF inhibits the increased endothelial permeability induced by irradiation and reverse the inhibitory effect of injured endothelial cells on hematopoietic stem cells and promote hematopoietic reconstruction.

中文翻译：

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PEDF促进骨髓内皮细胞损伤的修复，并加速骨髓移植后的造血重建。

骨髓移植之前的预处理（例如辐射）会引起血管内皮细胞损伤，促进受损血管内皮细胞的修复对造血重建很有帮助。色素上皮衍生因子（PEDF）调节血管通透性。但是，PEDF在预处理过程中修复受损内皮细胞的作用仍不清楚。我们的研究目的是研究PEDF对预处理诱导的内皮细胞损伤和造血重建的作用。在不存在或存在PEDF的情况下，将辐射诱导的内皮细胞与造血干细胞（HSC）共培养，然后分析HSC数量，细胞周期，集落形成和分化。此外，将PEDF注射到小鼠骨髓移植模型中，然后分析骨髓损伤，HSC数目和外周血造血重建以及细胞因子（SCF，TGF-β，IL-6和TNF-α）的分泌。两组之间的比较通过学生t检验进行，而多组通过单向或双向方差分析进行。受损的内皮细胞减少了HSC的扩增和集落的形成，诱导了HSC细胞周期的阻滞和凋亡，并促进了HSC的分化以及PEDF表达的降低。PEDF的添加增加了受损内皮细胞CD144的表达，并抑制了内皮通透性的增加，这在添加PEDF受体抑制剂Atglistatin后被取消了。此外，PEDF改善了受损的内皮细胞对体外HSC扩增的抑制作用。最后，PEDF促进了小鼠骨髓移植后的造血重建，并促进了SCF，TGF-β和IL-6的分泌。PEDF抑制辐射诱导的内皮通透性增加，并逆转受损的内皮细胞对造血干细胞的抑制作用，并促进造血重建。