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


OBJECTIVE
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.
Gambichler
T
T
Department of Dermatology, Ruhr-University Bochum, Gudrunstrasse 56, Bochum, Germany. t.gambichler@klinikum-bochum.de
Skrygan
M
M
Tomi
N S
NS
Breuksch
S
S
Altmeyer
P
P
Kreuter
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015536:Down-Regulation / Q000528:radiation effects; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects; D014467:Ultraviolet Therapy / Q000009:adverse effects
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta