Upregulation of MMP12 and its activity by UVA1 in human skin: potential implications for photoaging.
UVA1 constitutes around 75% of the terrestrial UV radiation, and most of the output of artificial tanning sources. However, the molecular effects of UVA1 in human skin in vivo are surprisingly poorly understood. We have examined time-dependent whole-genome expression, along with mRNA and protein changes in the skin after one minimal erythema dose of spectrally pure UVA1 (50 J cm(-2)) and 300 nm UVB (30 mJ cm(-2)). After 24 hours, the genes induced to the greatest extent were those involved in extracellular matrix remodeling with both UVA1 (P=5.5e-7) and UVB (P=2.9e-22). UVA1 and UVB caused different effects on matrix metalloproteinase (MMP) expression: UVB induced MMP1, MMP3, and MMP10 mRNA at 24 hours to a much greater extent than UVA1. MMP12 induction by UVA1 at 6 hours is marked and much greater than that by UVB. We have found that MMP12 mRNA induction by UVA1 resulted in expression of MMP12 protein, which is functional as an elastase. This induction of elastase activity did not occur with UVB. We hypothesize that the UVA1 induction of MMP12 mediates some of its photoaging effects, particularly by contributing to elastin degeneration in late solar elastosis. MMP12 is a good marker of UVA1 exposure.
King's College London, King's College London School of Medicine, Division of Genetics and Molecular Medicine, St John's Institute of Dermatology, London, UK. Electronic address: angela.tewari@kcl.ac.uk.
Angela
A
Tewari
St John's Institute of Dermatology, NIHR GSTFT/KCL Biomedical Research Centre, Guy's Hospital, London, UK.
Katarzyna
K
Grys
Bioinformatics, Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
Jutta
J
Kollet
King's College London, King's College London School of Medicine, Division of Genetics and Molecular Medicine, St John's Institute of Dermatology, London, UK.
Robert
R
Sarkany
King's College London, King's College London School of Medicine, Division of Genetics and Molecular Medicine, St John's Institute of Dermatology, London, UK.
Antony R
AR
Young
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053506:Matrix Metalloproteinase 10 / Q000235:genetics / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000235:genetics / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*; D015595:Skin Aging / Q000528:radiation effects*; D013997:Time Factors; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects*
D015415:Biomarkers; D012333:RNA, Messenger; D019278:Matrix Metalloproteinase 3; D053506:Matrix Metalloproteinase 10; D053508:Matrix Metalloproteinase 12; D020781:Matrix Metalloproteinase 1