Repeated exposure of human skin fibroblasts to UVB at subcytotoxic level triggers premature senescence through the TGF-β1 signaling pathway

Florence Debacq-Chainiaux, Céline Borlon, Thierry Pascal, Véronique Royer, François Eliaers, Noëlle Ninane, Géraldine Carrard, Bertrand Friguet, Françoise de Longueville, Sophie Boffe, José Remacle, Olivier Toussaint

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

Résumé

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.

langue originaleAnglais
Pages (de - à)743-758
Nombre de pages16
journalJournal of Cell Science
Volume118
Numéro de publication4
Les DOIs
Etat de la publicationPublié - 15 févr. 2005

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