A subset of human dermal fibroblasts overexpressing Cockayne syndrome group B protein resist UVB radiation-mediated premature senescence
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ABSTRACT: Ultraviolet B (UVB) radiation is a major contributor to skin photo-ageing. Although mainly absorbed by the epidermis, UVB photons managing to penetrate the upper dermis affect human dermal fibroblasts (HDFs), leading, among others, to the accumulation of senescent cells. In vitro studies have shown that repeated exposures to subcytotoxic UVB radiation doses provoke HDFs’ premature senescence shortly after the end of the treatment period. Here, we found that repetitive exposures to non-cytotoxic UVB radiation doses after several days lead to mixed cultures, containing both senescent cells and fibroblasts resisting senescence. “Resistant” fibroblasts were more resilient to a novel intense UVB radiation stimulus. RNA-seq analysis revealed that ERCC6, encoding Cockayne syndrome group B (CSB) protein, is upregulated in resistant HDFs compared to young and senescent cells, also confirmed at the protein level. CSB was found to be a key molecule conferring protection towards UVB cytotoxicity, as siRNA-mediated CSB loss-of-expression rendered HDFs significantly more susceptible to a high UVB radiation dose. In accordance, cells from a CSB-deficient patient were found to be dramatically more photosensitive. UVB-resistant HDFs remained normal (able to undergo replicative senescence) and non-tumorigenic. Even though they formed a distinct population in-between young and senescent cells, resistant HDFs retained numerous tissue-impairing characteristics of the senescence-associated secretory phenotype, including increased matrix metalloprotease activity and promotion of epidermoid tumor xenografts in immunodeficient mice. Collectively, here we describe a novel subpopulation of HDFs showing increased resistance to UVB-mediated premature senescence, as well as undesirable traits that may negatively affect skin homeostasis.
ORGANISM(S): Homo sapiens
PROVIDER: GSE268564 | GEO | 2025/03/19
REPOSITORIES: GEO
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