Identification of p53-dependent genes potentially involved in UVB-mediated premature senescence of human skin fibroblasts using siRNA technology

Mech Ageing Dev. 2008 Mar;129(3):109-19. doi: 10.1016/j.mad.2007.10.014. Epub 2007 Nov 9.

Abstract

Premature senescence of skin human diploid fibroblasts is induced after a series of 10 sublethal exposures to UVB at 2.5 kJ/m(2) with appearance of several biomarkers of cellular senescence like senescence-associated beta-galactosidase activity (SA beta-gal) and cell cycle arrest. Herein it is shown that the induction of UVB-induced premature senescence is associated with a transient increase of protein abundance and DNA-binding activity of p53. Silencing p53 expression with small interfering RNA (siRNA) affected the basal level of SA beta-gal and proliferative potential, but did not prevent UVB-induced increase of SA beta-gal and decrease of DNA synthesis. We used a senescence-specific low-density DNA array and p53 siRNA to study the mRNA abundance of 240 senescence-related genes and identified several potential p53-dependent genes differentially expressed after the repeated exposures to UVB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cellular Senescence / genetics*
  • DNA / metabolism
  • Fibroblasts / metabolism*
  • Fibroblasts / radiation effects
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Humans
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Skin / cytology
  • Skin / radiation effects*
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Ultraviolet Rays*
  • beta-Galactosidase / analysis

Substances

  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • DNA
  • beta-Galactosidase