title: Repeated exposure of human skin fibroblasts to UVB at subcytotoxic level triggers premature senescence through the TGF-beta1 signaling pathway.
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 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.
authors.affiliation: Laboratory of Biochemistry and Cellular Biology, Department of Biology, University of Namur (FUNDP), Rue de Bruxelles, 61, 5000 Namur, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Debacq-Chainiaux
authors.forename: Céline
authors.initials: C
authors.lastname: Borlon
authors.forename: Thierry
authors.initials: T
authors.lastname: Pascal
authors.forename: Véronique
authors.initials: V
authors.lastname: Royer
authors.forename: François
authors.initials: F
authors.lastname: Eliaers
authors.forename: Noëlle
authors.initials: N
authors.lastname: Ninane
authors.forename: Géraldine
authors.initials: G
authors.lastname: Carrard
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
authors.forename: Françoise
authors.initials: F
authors.lastname: de Longueville
authors.forename: Sophie
authors.initials: S
authors.lastname: Boffe
authors.forename: José
authors.initials: J
authors.lastname: Remacle
authors.forename: Olivier
authors.initials: O
authors.lastname: Toussaint
mesh_terms: D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D016922:Cellular Senescence; D051152:Clusterin; D004272:DNA, Mitochondrial / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D017384:Sequence Deletion; D015398:Signal Transduction; D012867:Skin / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D014466:Ultraviolet Rays; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C495242:CLU protein, human; D018797:Cell Cycle Proteins; D051152:Clusterin; D004272:DNA, Mitochondrial; D006023:Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D001616:beta-Galactosidase; D046988:Proteasome Endopeptidase Complex