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Particulate matter-induced senescence of skin keratinocytes involves oxidative stress-dependent epigenetic modifications

Authors
 Yea Seong Ryu  ;  Kyoung Ah Kang  ;  Mei Jing Piao  ;  Mee Jung Ahn  ;  Joo Mi Yi  ;  Guillaume Bossis  ;  Young-Min Hyun  ;  Chang Ook Park  ;  Jin Won Hyun 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.51(9) : 108, 2019 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
2019
Abstract
Ambient air particulate matter (PM) induces senescence in human skin cells. However, the underlying mechanisms remain largely unknown. We investigated how epigenetic regulatory mechanisms participate in cellular senescence induced by PM with a diameter <2.5 (PM2.5) in human keratinocytes and mouse skin tissues. PM2.5-treated cells exhibited characteristics of cellular senescence. PM2.5 induced a decrease in DNA methyltransferase (DNMT) expression and an increase in DNA demethylase (ten-eleven translocation; TET) expression, leading to hypomethylation of the p16INK4A promoter region. In addition, PM2.5 led to a decrease in polycomb EZH2 histone methyltransferase expression, whereas the expression of the epigenetic transcriptional activator MLL1 increased. Furthermore, binding of DNMT1, DNMT3B, and EZH2 to the promoter region of p16INK4A decreased in PM2.5-treated keratinocytes, whereas TET1 and MLL1 binding increased, leading to decreased histone H3 lysine 27 trimethylation (H3K27Me3) and increased H3K4Me3 in the promoter of p16INK4A. PM2.5-induced senescence involved aryl hydrocarbon receptor (AhR)-induced reactive oxygen species (ROS) production. ROS scavenging dampened PM2.5-induced cellular senescence through regulation of DNA and histone methylation. Altogether, our work shows that skin senescence induced by environmental PM2.5 occurs through ROS-dependent the epigenetic modification of senescence-associated gene expression. Our findings provide information for the design of preventive and therapeutic strategies against skin senescence, particularly in light of the increasing problem of PM2.5 exposure due to air pollution.
Files in This Item:
T201904389.pdf Download
DOI
10.1038/s12276-019-0305-4
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Park, Chang Ook(박창욱) ORCID logo https://orcid.org/0000-0003-3856-1201
Hyun, Young-Min(현영민) ORCID logo https://orcid.org/0000-0002-0567-2039
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173257
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