The gene expression profile of psoralen plus UVA-induced premature senescence in skin fibroblasts resembles a combined DNA-damage and stress-induced cellular senescence response phenotype.
After a finite number of population doublings, normal human cells undergo replicative senescence accompanied by growth arrest. We previously described a model of stress-induced premature senescence by treatment of dermal fibroblasts with psoralen plus UVA, a common photodermatological therapy. Psoralen photoactivation has long been used as a therapy for hyperproliferative skin disorders. The repetitive therapeutical treatment is accompanied by premature aging of the skin. Treatment of fibroblasts in vitro with 8-methoxypsoralen (8-MOP) and subsequent ultraviolet A (UVA) irradiation results in growth arrest with morphological and functional changes reminiscent of replicative senescence. For gene expression profiling in two strains of human skin fibroblasts after PUVA treatment, we used a low-density DNA array representing 240 genes involved in senescence and stress response. Twenty-nine genes were differentially expressed after PUVA treatment in the two strains of human skin fibroblasts. These genes are involved in growth arrest, stress response, modification of the extracellular matrix and senescence. This study contributes further to the elucidation of the PUVA model and its validation as a useful stress-induced premature senescence model aiming to characterize the premature senescence of fibroblasts and to identify biomarkers that could be applied in vivo.
Borlon
Céline
C
Research Unit on Cellular Biology (URBC), Department of Biology, University of Namur (FUNDP), Rue de Bruxelles, 61, B-5000 Namur, Belgium.
Debacq-Chainiaux
Florence
F
Hinrichs
Christina
C
Scharffetter-Kochanek
Karin
K
Toussaint
Olivier
O
Wlaschek
Meinhard
M
D019588:Aging, Premature / Q000235:genetics*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D016001:Confidence Intervals; D004249:DNA Damage; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D011564:Furocoumarins / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015595:Skin Aging / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D016326:Extracellular Matrix Proteins; D011564:Furocoumarins; D036341:Intercellular Signaling Peptides and Proteins; C515719:psoralen A