Modulation Of Selenium On Nitric Oxide Signaling In Human Mesenchymal Stem Cells And Umbilical Vein Endothelial Cells

The aims of the present study are:1) to investigate the regulation of selenium (Se) species to nitric oxide signaling in human mesenchymal stem cells(MSC), and 2) to clarify the effect of Se on angiogenesis of human umbilical vein endothelial cells in vitro. The main results have been obtained, which included:1. Supplementation of the inorganic selenium of sodium selenite [Na2SeO3, Se(IV)] inhibited the NOS activity and caused significant decreases of NO and ROS production in MSC, which showed a dose-dependent manner at 0.1-0.5μM of Se.2. The co-culture model of different radio of MSC:PBMC was used to detect the effect of Se on the PBMC proliferation in mixed lymphocyte reaction (MLR) with stimulation of mitogen (PHA). We found that treatments of Se (IV) at 0.1-0.5μM could significantly restore the MLR of immunosuppressive effect, which induced by MSC at the radio of MSC:PBMC at 1:5. We also demonstrated that Se(IV) treated MCS showed decreases of expression of iNOS,eNOS and Nrf2 as well as NO and ROS production.3.Se-Met significantly up-regulated NO production in HUVEC by dose-dependent manner with treatments of 0.1μmol/L and 0.5μmol/L at 24 h compared with the control group, while inhibited NO production in HUVEC with treatment of 1μmol/L and 5μmol/L at 24 h.4. An in vitro experiment for angiogenesis of HUVEC was performed in this study. Cultured HUVECs are seeded onto the commercially available Matrigel. The integrity of the tubing network in the group pretreated with 0.1μmol/L Se-Met remained intact. Furthermore, this enhanced tubular formation network was also reflected in 0.5μmol/L Se-Met -treated groups. Concentrations of 1μmol/L and 5μmol/L seemed to hamper the induction of tubing morphogenesis and the integrity of tubings compared with the control group.In conclusion, Se(IV) supplementation (0.1-0.5μM) displayed obvious antagonistic action on suppression of T cell proliferation induced by MSC and Se-Met could affect the angiogenesis process of HUVEC in vitro through NO signaling pathways, and then modulate the physiological functions.