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

Experimental & Molecular Medicine 2019년 51권 9호 p.108 ~ 108
 ( Ryu Yea-Seong ) - Jeju National University School of Medicine Jeju Research Center for Natural Medicine

 ( Kang Kyoung-Ah ) - Jeju National University School of Medicine Jeju Research Center for Natural Medicine
 ( Piao Mei Jing ) - Jeju National University School of Medicine Jeju Research Center for Natural Medicine
 ( Ahn Mee-Jung ) - Jeju National University College of Veterinary Medicine
 ( Yi Joo-Mi ) - Inje University College of Medicine Department of Microbiology and Immunology
 ( Bossis Guillaume ) - University of Montpellier Institut de Genetique Moleculaire de Montpellier
 ( Hyun Young-Min ) - Yonsei University College of Medicine Department of Anatomy
 ( Park Chang-Ook ) - Yonsei University College of Medicine Department of Dermatology
 ( Hyun Jin-Won ) - Jeju National University School of Medicine Jeju Research Center for Natural Medicine

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.

키워드

Biochemistry; Cell biology
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