Repeated exposures to UVB induce differentiation rather than senescence of human keratinocytes lacking p16INK-4A

Véronique Vallery, Emmanuelle Boilan, Noëlle Ninane, Catherine Demazy, Bertrand Friguet, Olivier Toussaint, Yves Poumay, Florence Debacq-Chainiaux

Research output: Contribution to journalArticle

Abstract

Skin cancers and extrinsic aging are delayed consequences of cumulative UV radiation insults. Exposure of human keratinocytes to UVB has been previously shown to trigger premature senescence. In order to explore the involvement of the cyclin-dependent kinase inhibitor p16INK-4a in UVB-induced premature senescence, we developed an original model of repeated sublethal exposures of human keratinocytes deficient in p16INK-4a We did not observe any significant increase of senescence-associated β-galactosidase activity positive cells following UVB exposure in this cell line in contrast to primary keratinocytes, suggesting a role for p16INK-4a in UVB-induced senescence. However, we detected sustained DNA damage, prolonged cell cycle arrest, and induction of markers of epidermal differentiation like involucrin and filaggrin as consequences of the repeated exposures. Keratinocytes exposed to the same dose of UVB in a single exposure died. Furthermore, the abundance of the keratins 6, 16 and 17 was increased in keratinocytes exposed repeatedly to UVB suggesting an alternative differentiation. This model allows the induction of a state of differentiation observed in vivo with differentiation uncoupled from premature senescence.

Original languageEnglish
Pages (from-to)167-181
Number of pages15
JournalBiogerontology
Volume11
Issue number2
DOIs
Publication statusPublished - 1 Apr 2010

Keywords

  • Differentiation
  • DNA damage
  • Keratinocytes
  • UVB Senescence

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