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Human dermal fibroblasts escape from the long-term phenocopy of senescence induced by psoralen photoactivation.

Abstract：

: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.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Ma W,Wlaschek M,Brenneisen P,Schneider LA,Hommel C,Hellweg C,Sauer H,Wartenberg M,Herrmann G,Meewes C,Boukamp P,Scharffetter-Kochanek K

doi

10.1006/excr.2002.5476

keywords:

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

299-309

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014482702954765

journal_volume

274

pub_type

杂志文章

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