The effect of ultraviolet radiation on the transforming growth factor beta 1/Smads pathway and p53 in actinic keratosis and normal skin

Arch Dermatol Res. 2013 Nov;305(9):777-86. doi: 10.1007/s00403-013-1361-6. Epub 2013 Apr 30.

Abstract

Ultraviolet (UV) radiation is considered to be essential for the progression of actinic keratosis (AK) to squamous cell carcinoma (SCC); however, the mechanisms have not been fully elucidated. To understand this process, the effects of UV radiation on the transforming growth factor beta 1 (TGFβ1)/Smads pathway and p53 in normal skin and AK were studied. Normal human skin and AK tissues were cultured and divided into the following four groups according to the UV radiation dose: 0 (control group), 5, 10, and 20 J/cm2. The tissues were radiated for four consecutive days; 24 h after radiation, the tissues were collected for investigation. Compared with the control group, greater proliferative inhibition and apoptosis were induced by UV radiation in normal skin than AK. The expression of TGFβ1, Smad7, and p53 was increased in AK and normal skin, while the level of TβRII was decreased. Smad2 was reduced in AK only. The expressions of TβRI, Smad3, and Smad4 were not significantly changed. The results demonstrated that although p53 was induced, suppression of the TGFβ1/Smads pathway by UV radiation might contribute to the progression of AK to SCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • Cell Proliferation / radiation effects
  • Cells, Cultured
  • Humans
  • Keratosis, Actinic / metabolism*
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Serine-Threonine Kinases / radiation effects
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / biosynthesis
  • Receptors, Transforming Growth Factor beta / metabolism
  • Receptors, Transforming Growth Factor beta / radiation effects
  • Skin / radiation effects
  • Smad Proteins / biosynthesis
  • Smad Proteins / metabolism*
  • Smad Proteins / radiation effects
  • Smad2 Protein / biosynthesis
  • Smad2 Protein / metabolism
  • Smad2 Protein / radiation effects
  • Smad3 Protein / biosynthesis
  • Smad3 Protein / metabolism
  • Smad3 Protein / radiation effects
  • Smad4 Protein / biosynthesis
  • Smad4 Protein / metabolism
  • Smad4 Protein / radiation effects
  • Smad7 Protein / biosynthesis
  • Smad7 Protein / metabolism
  • Smad7 Protein / radiation effects
  • Transforming Growth Factor beta1 / biosynthesis
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta1 / radiation effects
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Protein p53 / radiation effects
  • Ultraviolet Rays / adverse effects*

Substances

  • Receptors, Transforming Growth Factor beta
  • SMAD2 protein, human
  • SMAD3 protein, human
  • SMAD4 protein, human
  • SMAD7 protein, human
  • Smad Proteins
  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • Smad7 Protein
  • Transforming Growth Factor beta1
  • Tumor Suppressor Protein p53
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II