Involvement of reactive oxygen species in TGF-beta1-induced tropoelastin expression by human dermal fibroblasts.
Chronic exposure to solar UV radiation causes marked changes in the dermal extracellular matrix that underlie the loss of resiliency and increased laxity observed in photoaged skin. In particular, the dermal elastin content increases substantially and the normal, well-organized elastic fibers are replaced by amorphous elastotic material. Transforming growth factor-beta1 (TGF-beta1) stimulates synthesis of elastin by dermal fibroblasts and may mediate the increase in elastin in chronically photodamaged skin. We investigated pathways involved in the TGF-beta1-induced increase in tropoelastin (TE), the soluble elastin monomer and assessed the role of reactive oxygen species (ROS) in the regulation of TE mRNA. Antioxidants and an inhibitor of NADPH oxidase blocked TGF-beta1-induced TE mRNA increase even when added 1.5 h after TGF-beta1, although ROS were detected for only 30 min. The TE mRNA increase required activation of Smad4, shown using Smad4 siRNA, and also involved the ERK1/2, p38 and JNK MAP kinases but not PI3K. ROS did not enhance signaling through Smad2 but did enhance activation of p38 and ERK1/2 at 10 min after TGF-beta1. These results indicate that Smad and MAPK pathways mediate TGF-beta1-induced TE expression and that ROS are required for both early signal transduction and later steps that increase elastin.
Choi
Won Seon
WS
Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Mitsumoto
Atsushi
A
Kochevar
Irene E
IE
D002478:Cells, Cultured; D020405:Dermis / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014333:Tropoelastin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D014333:Tropoelastin