High-glucose induced HIF-1α down-regulation impairs the function of the endothelial progenitor cells via PI3K/AKT signaling pathway

Abstract

Objective: This study aimed to investigate the effect of high-glucose conditions in the EPCs from whole peripheral and bone marrow of diabetic rats. To determine the expression of critical initiation factor HIF-1 α and HIF-1 α -induced vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) in high glucose environment. The effect of over expression of HIF-1 α to the function of the EPCs in diabetic rats via regulating PI3K/AKT signaling pathway. Methods: Primary EPCs from whole peripheral and bone marrow of Sprague-Dawley control rats and streptozoctin (STZ)-induced diabetic rats were harvested, isolated and characterized. Cell viability, migration, and tube formation ability were detected by CCK8, Transwell assay and Matrigel-based capillary-like tube formation assay. Gene transcription and protein expression were evaluated by real-time polymerase chain reaction and Western blotting, respectively. Results: Cell viability, migration, and tube formation ability of EPCs were impaired under high-glucose conditions. Overexpression of HIF-1 α alleviated high glucose-induced EPCs dysfunction by promoting the transcription and expression of VEGF and VEGFR in EPCs under high-glucose. Furthermore, high-glucose inhibited PI3K/AKT phosphorylation and PI3K agonist rescued the HIF-1 α -VEGF/VEGFR expression of EPCs under high-glucose conditions via activating PI3K/AKT signaling pathway. Conclusion: These results suggest that the attenuation of high-glucose induced EPCs dysfunction of diabetic rats by HIF-1 α overexpression partly requires activating PI3K/AKT signaling pathway, thus providing theoretical basis for the treatment of diabetic vascular neogenesis and vascular injury repair.