Repeated exposure of human skin fibroblasts to UVB at subcytotoxic level triggers premature senescence through the TGF-beta1 signaling pathway

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...

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Veröffentlicht in:Journal of cell science 2005-02, Vol.118 (Pt 4), p.743-758
Hauptverfasser: Debacq-Chainiaux, Florence, Borlon, Céline, Pascal, Thierry, Royer, Véronique, Eliaers, François, Ninane, Noëlle, Carrard, Géraldine, Friguet, Bertrand, de Longueville, Françoise, Boffe, Sophie, Remacle, José, Toussaint, Olivier
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Sprache:eng
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Zusammenfassung: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 so-called biomarkers of senescence were markedly expressed: growth arrest, senescence-associated beta-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-beta1 (TGF-beta1). Transfection of apo J cDNA provided protection against premature senescence-inducing doses of UVB and other stressful agents. Neutralizing antibodies against TGF-beta1 or its receptor II (TbetaRII) sharply attenuated the senescence-associated features, suggesting a role for TGF-beta1 in UVB-induced premature senescence. Both the latent and active forms of TGF-beta1 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.
ISSN:0021-9533