Vascular endothelial growth factor receptor 2 (VEGFR2, Flk-1/KDR) protects HEK293 cells against CoCl 2-induced hypoxic toxicity

摘要

Vascular endothelial growth factor (VEGF) is an endothelium-specific mitogen and a promising inducer of angiogenesis and lymphangiogenesis. The VEGF receptors on endothelial cell membrane include the tyrosine kinases VEGFR-1 (Flt-1), VEGFR-2 (Flk-1/KDR) and VEGFR-3 (Flt-4). KDR is a major mediator of mitogenic, angiogenic and permeability-enhancing effects of VEGF. KDR is upregulated in response to hypoxia, a major inducer of VEGF gene transcription. A HEK293 cell line overexpressing KDR was established under cell hypoxic stress to explore the function of KDR. A hypoxia-inducing agent, cobalt chloride (CoCl 2) was applied to detect whether KDR was able to prevent against chemical hypoxic toxicity. The results indicate that KDR attenuated CoCl 2-induced cell injury in HEK293 cells. Furthermore, the underlying mechanisms may be explained by the increased expression of Bcl-2, AKT1 and phosphorylated AKT, key members of cell survival pathway, and decreased expression of pro-apoptosis protein Bax.