Abstract
Premature senescence of human diploid fibroblasts (HDFs) can be induced by exposures to a variety of oxidative stress and DNA damaging agents. In this study we developed a robust model of UVB-induced premature senescence of skin HDFs. After a series of 10 subcytotoxic (non-proapoptotic) exposures to UVB at 250 mJ/cm2, the socalled biomarkers of senescence were markedly expressed: growth arrest, senescence-associated β-galactosidase activity, senescence-associated gene overexpression, deletion in mitochondrial DNA. A set of 44 stress- and senescence-associated genes were found to be differentially expressed in this model, among which clusterin/apolipoprotein J (apo J) and transforming growth factor-β1 (TGF-β1). Transfection of apo J cDNA provided protection against premature senescence-inducing doses of UVB and other stressful agents. Neutralizing antibodies against TGF-β1 or its receptor II (TβRII) sharply attenuated the senescence-associated features, suggesting a role for TGF-β1 in UVB-induced premature senescence. Both the latent and active forms of TGF-β1 were increased with time after the last UVB stress. Proteasome inhibition was ruled out as a potential mechanism of UVB-induced stress-induced premature senescence (SIPS). This model represents an alternative in vitro model in photoaging research for screening potential anti-photoaging compounds.
Original language | English |
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Pages (from-to) | 743-758 |
Number of pages | 16 |
Journal | Journal of Cell Science |
Volume | 118 |
Issue number | 4 |
DOIs | |
Publication status | Published - 15 Feb 2005 |
Keywords
- Clusterin
- Fibroblasts
- Proteasome
- Protein oxidation
- Senescence
- Transforming growth factor beta-1
- UVB