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

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 dur...

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Main Authors: Ju Hwan Kim, Dong-Jun Kang, Jun-Sang Bae, Jai Hyuen Lee, Sangbong Jeon, Hyung-Do Choi, Nam Kim, Hyung-Gun Kim, Hak Rim Kim
Format: Article
Language:English
Published: Nature Portfolio 2021-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-87263-2
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author Ju Hwan Kim
Dong-Jun Kang
Jun-Sang Bae
Jai Hyuen Lee
Sangbong Jeon
Hyung-Do Choi
Nam Kim
Hyung-Gun Kim
Hak Rim Kim
author_facet Ju Hwan Kim
Dong-Jun Kang
Jun-Sang Bae
Jai Hyuen Lee
Sangbong Jeon
Hyung-Do Choi
Nam Kim
Hyung-Gun Kim
Hak Rim Kim
author_sort Ju Hwan Kim
collection DOAJ
description 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.
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spelling doaj.art-cd61121e2bb24059ae0227d2b5292b9f2022-12-21T19:33:06ZengNature PortfolioScientific Reports2045-23222021-04-0111111010.1038/s41598-021-87263-2Activation of matrix metalloproteinases and FoxO3a in HaCaT keratinocytes by radiofrequency electromagnetic field exposureJu Hwan Kim0Dong-Jun Kang1Jun-Sang Bae2Jai Hyuen Lee3Sangbong Jeon4Hyung-Do Choi5Nam Kim6Hyung-Gun Kim7Hak Rim Kim8Department of Pharmacology, College of Medicine, Dankook UniversityDepartment of Pharmacology, College of Medicine, Dankook UniversityMedical Laser Research Center, Dankook UniversityDepartment of Nuclear Medicine, College of Medicine, Dankook UniversityRadio and Broadcasting Technology Laboratory, ETRIRadio and Broadcasting Technology Laboratory, ETRISchool of Electrical and Computer Engineering, Chungbuk National UniversityDepartment of Pharmacology, College of Medicine, Dankook UniversityDepartment of Pharmacology, College of Medicine, Dankook UniversityAbstract 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.https://doi.org/10.1038/s41598-021-87263-2
spellingShingle Ju Hwan Kim
Dong-Jun Kang
Jun-Sang Bae
Jai Hyuen Lee
Sangbong Jeon
Hyung-Do Choi
Nam Kim
Hyung-Gun Kim
Hak Rim Kim
Activation of matrix metalloproteinases and FoxO3a in HaCaT keratinocytes by radiofrequency electromagnetic field exposure
Scientific Reports
title Activation of matrix metalloproteinases and FoxO3a in HaCaT keratinocytes by radiofrequency electromagnetic field exposure
title_full Activation of matrix metalloproteinases and FoxO3a in HaCaT keratinocytes by radiofrequency electromagnetic field exposure
title_fullStr Activation of matrix metalloproteinases and FoxO3a in HaCaT keratinocytes by radiofrequency electromagnetic field exposure
title_full_unstemmed Activation of matrix metalloproteinases and FoxO3a in HaCaT keratinocytes by radiofrequency electromagnetic field exposure
title_short Activation of matrix metalloproteinases and FoxO3a in HaCaT keratinocytes by radiofrequency electromagnetic field exposure
title_sort activation of matrix metalloproteinases and foxo3a in hacat keratinocytes by radiofrequency electromagnetic field exposure
url https://doi.org/10.1038/s41598-021-87263-2
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