In vivo identification of solar radiation-responsive gene network: role of the p38 stress-dependent kinase.
Solar radiation is one of the most common threats to the skin, with exposure eliciting a specific protective cellular response. To decrypt the underlying mechanism, we used whole genome microarrays (Agilent 44K) to study epidermis gene expression in vivo in skin exposed to simulated solar radiation (SSR). We procured epidermis samples from healthy Caucasian patients, with phototypes II or III, and used two different SSR doses (2 and 4 J/cm(2)), the lower of which corresponded to the minimal erythemal dose. Analyses were carried out five hours after irradiation to identify early gene expression events in the photoprotective response. About 1.5% of genes from the human genome showed significant changes in gene expression. The annotations of these affected genes were assessed. They indicated a strengthening of the inflammation process and up-regulation of the JAK-STAT pathway and other pathways. Parallel to the p53 pathway, the p38 stress-responsive pathway was affected, supporting and mediating p53 function. We used an ex vivo assay with a specific inhibitor of p38 (SB203580) to investigate genes the expression of which was associated with active p38 kinase. We identified new direct p38 target genes and further characterized the role of p38. Our findings provide further insight into the physiological response to UV, including cell-cell interactions and cross-talk effects.
Mouchet
Nicolas
N
CNRS UMR 6061 Institut de Génétique et Développement de Rennes, Equipe RTO, Rennes, France.
Adamski
Henri
H
Bouvet
Régis
R
Corre
Sébastien
S
Courbebaisse
Yann
Y
Watier
Eric
E
Mosser
Jean
J
Chesné
Christophe
C
Galibert
Marie-Dominique
MD
D002877:Chromosomes, Human / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects; D053263:Gene Regulatory Networks / Q000528:radiation effects*; D006801:Humans; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects; D012867:Skin / Q000201:enzymology / Q000528:radiation effects; D013472:Sunlight; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D048051:p38 Mitogen-Activated Protein Kinases