Cytochrome P450 genes play central roles in transcriptional response by keratinocytes to a high-voltage alternating current electric field.

The endogenous electric field (EF) of skin wounds plays an important role in the biological processes that underlie wound healing. Treatments that modulate wound-EFs promote healing. However, the mechanism(s) that underlie this effect remain unclear. Agilent-based microarrays were used to determine the transcriptomes of the keratinocyte line HaCaT, normal human dermal fibroblasts, and the human dermal endothelial cell line HMEC-1 before and after high-voltage alternating current (AC)-EF (14,000 V, 90 Hz) treatment. The keratinocytes had the most genes whose transcription was altered by EF. They included the cytochrome P450 (CYP) genes CYP1A1 and CYP1B1, HMOX1, EREG, DUSP5, and SLC7A11 (all upregulated), and DOCK8, ABCC6, and CYP26A1 (all downregulated). As shown by transcriptional-network analysis, all three CYP genes played central roles in the EF-induced changes in keratinocyte transcriptome. To the best of our knowledge, this is the first study that demonstrates that CYP genes play a key role in the transcriptional responses of human keratinocytes to EF treatment. Further investigations into the effects of EF on wound healing, aging, and regenerative medicine are likely to yield promising results.