Human dermal fibroblasts escape from the long-term phenocopy of senescence induced by psoralen photoactivation.
We have previously shown that following psoralen photoactivation (PUVA treatment) human dermal fibroblasts undergo long-term growth arrest as well as morphological and functional changes reminiscent of cellular senescence [ 1 ]. In the absence of molecular data on what constitutes normal senescence, it has been difficult to decide whether these PUVA-induced changes reflect cellular senescence or rather a mimic thereof. We herein report that PUVA-induced growth arrest, the senescent phenotype with long-term induction of senescence-associated beta-galactosidase, as well as increased expression of matrix metalloprotease-1 are fully reversible at days 100 to 130 post PUVA treatment in four independently tested fibroblast strains. The late returning growth capacity in PUVA-treated fibroblasts is not due to immortalization, as shown by continued lack of telomerase activity, accelerated telomere shortening, and a decrease in overall growth rates in fibroblasts in their regrowing phase post PUVA treatment. Lack of anchorage-independent growth additionally suggests that the cells are also not tumorigenically transformed. Collectively, our data suggest that PUVA-induced changes do not fully reflect replicative senescence but rather represent a long-term transient phenocopy of senescence. The model reported here is particularly suited to elucidating mechanisms underlying long-term transient growth arrest, the related functional changes, and the release of cells thereof.
Ma
Wenjian
W
Department of Dermatology, University of Cologne, Joseph-Stelzmann-Strasse 9, Germany.
Wlaschek
Meinhard
M
Brenneisen
Peter
P
Schneider
Lars Alexander
LA
Hommel
Christina
C
Hellweg
Christine
C
Sauer
Heinrich
H
Wartenberg
Maria
M
Herrmann
Gernot
G
Meewes
Christian
C
Boukamp
Petra
P
Scharffetter-Kochanek
Karin
K
D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D020405:Dermis / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D011701:PUVA Therapy / Q000009:adverse effects*; D010641:Phenotype; D012871:Skin Diseases / Q000188:drug therapy*; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology; D019098:Telomerase / Q000187:drug effects / Q000378:metabolism; D016615:Telomere / Q000187:drug effects / Q000378:metabolism; D001616:beta-Galactosidase / Q000187:drug effects / Q000378:metabolism
D019098:Telomerase; D001616:beta-Galactosidase; D020781:Matrix Metalloproteinase 1