Direct Current Electrical Fields Improve Experimental Wound Healing by Activation of Cytokine Secretion and Erk1/2 Pathway Stimulation

Abstract

There is growing evidence that cell behaviors can be influenced by the direct current electric fields (EFs). Some behaviors may influence wound healing directly. This study aimed to investigate the effects of EF (200 mV/mm) on immortalized nontumorigenic human epidermal (HaCaT) cells. We established a setup that can transmit an EF and maintain a stable cell culture environment. An EF was applied to HaCaT cells, and scratch-assays were performed as a model of wound healing to observe cell migration. Proliferation was evaluated by mitochondrial activity, total protein, and DNA content. Secretion of healing-associated cytokines was evaluated via cytokine arrays, and Western blot was applied to investigate signaling pathway alterations. Compared with the control group, the migration of cells exposed to EFs significantly increased (p < 0.01). After 7 days, the changes in proliferation also increased significantly (p < 0.05). The cytokine arrays revealed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was the most abundant factor secreted by HaCaT following EF exposure. The signals for phospho-Erk1/2 showed a significant (p < 0.0001) increase following EF exposure. The results demonstrate that exposure of HaCaT cells to EFs has positive effects on migration, proliferation, and cytokine secretion—three important steps in wound healing—and these effects may be partially mediated by activation of the Erk1/2 signaling pathway.