Hypoxic preconditioning promotes galvanotaxis of human dermal microvascular endothelial cells through NF-κB pathway

Angiogenesis plays an important role in wound healing, especially in chronic wound. The directional migration of the human dermal microvascular endothelial cells (HDMECs) is the key regulation of angiogenesis. The wound healing can be regulated by numerous microenvironment factors including the electric fields, hypoxia and chemotaxis. During wound repair, the electric fields mediates the directional migration of cells and the hypoxia, which occurs immediately after injury, acts as an early stimulus to initiate the healing process. However, the mechanism of hypoxia and the endogenous electric fields coordinating to promote angiogenesis remain elusive. In this study, we observed the effect of hypoxia on the directional migration of HDMECs under electric fields. The galvanotaxis of HDMECs under the electric fields (200 mV/mm) was significantly improved, and the expression of VEGF/VEGFR2 was up-regulated after 4h of hypoxic preconditioning. In addition, the knockdown of VEGFR2 reversed the directivity of HDMECs promoted by hypoxia in the electric fields. Moreover, knockdown of VEGFR2 inhibited the migration directionality of HDMECs in the electric field after hypoxic preconditioning. Hypoxia decreased the activation of NF-κB in HDMECs. Activated NF-κB by fusicoccin decreased the expression of VEGFR2/VEGF and negatively regulated the migration direction of HDMECs in the electric fields. Enhancing the galvanotaxis response of cells might therefore be a clinically attractive approach to induce improved angiogenesis.