Gynecology Research Unit, Hannover Medical School, Hannover, Germany.
Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
FASEB J. 2019 Aug;33(8):9142-9153. doi: 10.1096/fj.201802750RR. Epub 2019 May 14.
Endothelial colony-forming cells (ECFCs), a proliferative subpopulation of endothelial progenitor cells, are involved in angiogenesis and endothelial repair. In this study, we investigated endothelial barrier characteristics of ECFCs, whether vitamin D supports cell-cell adhesion and barrier integrity, and how it affects ECFC mobilization and actin dynamics. Although ECFC barrier was disrupted under inflammatory conditions, this effect was rescued by vitamin D treatment, leading to higher stability of an ECFC monolayer. Furthermore, vitamin D enhanced ECFC mobilization toward directional migration. In addition, immunocytochemistry, quantitative real-time PCR, and immunoblotting analysis showed that vitamin D increased endothelial interconnections through vascular endothelial cadherin (VE-cadherin) junctions and by impacting cell dynamics through cofilin and VE-cadherin phosphorylation. Our results suggest that vitamin D treatment efficiently counteracts inflammation in an ECFC monolayer, resulting in higher ECFC barrier integrity. This study provides evidence of a new beneficial effect of vitamin D for ECFC homeostasis.-Schröder-Heurich, B., von Hardenberg, S., Brodowski, L., Kipke, B., Meyer, N., Borns, K., von Kaisenberg, C. S., Brinkmann, H., Claus, P., von Versen-Höynck, F. Vitamin D improves endothelial barrier integrity and counteracts inflammatory effects on endothelial progenitor cells.
内皮祖细胞(Endothelial Progenitor Cells,EPCs)的一个增殖亚群,内皮集落形成细胞(Endothelial Colony-Forming Cells,ECFCs)参与血管生成和内皮修复。在本研究中,我们研究了 ECFC 的内皮屏障特性、维生素 D 是否支持细胞-细胞黏附和屏障完整性,以及它如何影响 ECFC 的动员和肌动蛋白动力学。尽管 ECFC 屏障在炎症条件下被破坏,但维生素 D 处理可挽救这种效应,导致 ECFC 单层的稳定性更高。此外,维生素 D 增强了 ECFC 向定向迁移的动员。此外,免疫细胞化学、实时定量 PCR 和免疫印迹分析表明,维生素 D 通过血管内皮钙黏蛋白(VE-cadherin)连接增加内皮细胞的连接,并通过影响原肌球蛋白和 VE-cadherin 的磷酸化来影响细胞动力学。我们的结果表明,维生素 D 处理有效地对抗 ECFC 单层中的炎症,导致更高的 ECFC 屏障完整性。本研究为维生素 D 对 ECFC 动态平衡的有益作用提供了证据。