Significant downregulation of transforming growth factor-beta signal transducers in human skin following ultraviolet-A1 irradiation

Br J Dermatol. 2007 May;156(5):951-6. doi: 10.1111/j.1365-2133.2007.07802.x. Epub 2007 Mar 23.

Abstract

Background: Despite the significant role of the transforming growth factor (TGF)-beta/Smad pathway in cell growth and extracellular matrix regulation, relatively little is known regarding the effect of ultraviolet (UV) radiation on the TGF-beta/Smad signalling in human skin.

Objectives: We aimed to investigate the impact of UVA1 and UVB on the mRNA and protein expression of TGF-beta/Smad signal transducers in human skin in vivo.

Methods: Fifteen subjects were exposed to 1.5 minimal erythema doses (MED) (4.5 MED cumulative) of UVA1 and UVB over a 3-day period. Skin biopsies were obtained at 24 and 72 h after the last UV exposure. Real-time reverse transcription-polymerase chain reaction and immunohistology were performed.

Results: In the UVA1-exposed sites (24 h, 72 h), mRNA expression of TGF-beta1 and Smad3/4/7 was significantly downregulated as compared with nonirradiated skin sites (P < 0.05). At 24 h, immunohistology revealed significantly reduced TGF-beta1 protein levels in fibroblasts (P < 0.05). However, mRNA and protein expression of TGF-beta/Smad proteins observed in UVB-irradiated sites did not differ significantly from control sites (P > 0.05).

Conclusions: In contrast to UVB, UVA1 significantly downregulates the expression of TGF-beta/Smad proteins in human skin in vivo. The extent to which the acute effects of TGF-beta/Smad signalling reported in the present paper are related to the beneficial effect of UVA1-based phototherapy of fibrotic skin conditions and/or to the chronic effects of UV that result in photoaging and cancer remains to be established.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Down-Regulation* / radiation effects
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects*
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • RNA, Messenger / radiation effects
  • Signal Transduction / radiation effects
  • Skin / metabolism
  • Skin / radiation effects
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / radiation effects
  • Ultraviolet Rays / adverse effects
  • Ultraviolet Therapy / adverse effects

Substances

  • RNA, Messenger
  • Transforming Growth Factor beta