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Series GSE45493 Query DataSets for GSE45493
Status Public on May 15, 2014
Title MMP12 is induced by UVA1 in vivo in humans
Organism Homo sapiens
Experiment type Expression profiling by array
Summary UVA1 makes up ~75% terrestrial ultraviolet radiation (UVR) is increasingly being used for the treatment for inflammatory skin disorders. It is also the major UVR spectral source in tanning lamps, however we lack human data to understand its effects on gene expression and further consequences. Using erythemally equivalent doses of UVA1 (50J/cm2) and UVB (30mJ/cm2) ~1MED (minimal erythema dose), this study examines time dependent whole genome expression, mRNA and protein changes in 12 skin types I/II individuals. The top upregulated pathway at 6h is inflammation through IL17 signaling for UVA1 (p=1.16e-6) and UVB (p=2.1e-4). At 24h the top upregulated pathway is extracellular matrix remodeling for UVA1 (p=5.5e-7) and UVB (p=2.9e-22). We show key spectral differences with matrix metalloproteinases (MMP): UVB upregulates MMP1 mRNA (p=0.0062), MMP3 mRNA (p=0.0016), MMP10 mRNA (p=0.028) at 24h compared to UVA1, MMP12 mRNA is upregulated by UVA1 at 6h and not by UVB (p=0.02). In a further 3 skin type I/II we show that MMP12 protein is formed by UVA1 (p=0.04) at 24h and that DQ™ collagen type IV(likely MMP12 activity) hydrolysis occurs by UVA1 (p=0.027) at 10h. DQ™ collagen type I hydrolysis occurs predominantly by UVB at 24h (p=0.031). Both UVA1 and UVB upregulate MMP1 at 10h and 24h. There is more MMP1 and MMP12 protein and activity in the epidermis than in dermis in all volunteers. We conclude that the biological processes that occur after 24h in human skin in vivo in response to erythemally equivalent doses of UVA1 and UVB are similar however there are key spectral differences: UVB plays a larger role in upregulating key MMPs in the epidermis. MMP12 is a UVA1 specific biomarker found predominantly in the epidermis and maybe useful as a marker of UVA1 exposure. We hypothesise that its formation by UVA1 could be related to the ability of UVA1 to produce significantly more oxidatively generated DNA than UVB (8oxodG).
 
Overall design 47 samples were processed. The RNA was isolated from human skin samples of individual donors pre- or post irradiation with UVA or UVB. Skin biopsies were taken either before, 6h post, or 24h post exposure. Different doses of UVA were applied. Each condition was available from five or nine individuals, as indicated in the samples description below.
 
Contributor(s) Tewari A, Grys K, Sarkany R, Young AR
Citation(s) 24714202, 31529490
Submission date Mar 26, 2013
Last update date Jul 07, 2020
Contact name Angela Tewari
E-mail(s) angela.tewari@kcl.ac.uk
Organization name King`s College London
Department St. John's Institute of Dermatology
Lab Dermatolgy
Street address 9th Floor Tower Wing, Guys Hospital
City London
ZIP/Postal code SEI 9RT
Country United Kingdom
 
Platforms (1)
GPL6480 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version)
Samples (47)
GSM1105593 control (A_4C)
GSM1105594 control (A_5C)
GSM1105595 control (A_6C)
Relations
BioProject PRJNA194390

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE45493_RAW.tar 423.0 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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