Activation of matrix metalloproteinases and FoxO3a in HaCaT keratinocytes by radiofrequency electromagnetic field exposure

Sci Rep. 2021 Apr 7;11(1):7680. doi: 10.1038/s41598-021-87263-2.

Abstract

As the skin is the largest body organ and critically serves as a barrier, it is frequently exposed and could be physiologically affected by radiofrequency electromagnetic field (RF-EMF) exposure. In this study, we found that 1760 MHz RF-EMF (4.0 W/kg specific absorption rate for 2 h/day during 4 days) exposure could induce intracellular reactive oxygen species (ROS) production in HaCaT human keratinocytes using 2',7'-dichlorofluorescin diacetate fluorescent probe analysis. However, cell growth and viability were unaffected by RF-EMF exposure. Since oxidative stress in the skin greatly influences the skin-aging process, we analyzed the skin senescence-related factors activated by ROS generation. Matrix metalloproteinases 1, 3, and 7 (MMP1, MMP3, and MMP7), the main skin wrinkle-related proteins, were significantly increased in HaCaT cells after RF-EMF exposure. Additionally, the gelatinolytic activities of secreted MMP2 and MMP9 were also increased by RF-EMF exposure. FoxO3a (Ser318/321) and ERK1/2 (Thr 202/Tyr 204) phosphorylation levels were significantly increased by RF-EMF exposure. However, Bcl2 and Bax expression levels were not significantly changed, indicating that the apoptotic pathway was not activated in keratinocytes following RF-EMF exposure. In summary, our findings show that exposure to 1760 MHz RF-EMF induces ROS generation, leading to MMP activation and FoxO3a and ERK1/2 phosphorylation. These data suggest that RF-EMF exposure induces cellular senescence of skin cells through ROS induction in HaCaT human keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electromagnetic Fields / adverse effects*
  • Enzyme Activation / radiation effects
  • Forkhead Box Protein O3 / metabolism*
  • HaCaT Cells
  • Humans
  • Keratinocytes / enzymology
  • Keratinocytes / radiation effects*
  • MAP Kinase Signaling System / radiation effects
  • Matrix Metalloproteinases / metabolism*
  • Phosphorylation / radiation effects
  • Radio Waves / adverse effects
  • Reactive Oxygen Species / metabolism
  • Skin Aging / radiation effects*

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Reactive Oxygen Species
  • Matrix Metalloproteinases