Changes of MMP-1 and collagen type Ia1 by UVA, UVB and IRA are differentially regulated by Trx-1 Nicole Buechner 1 , Peter Schroeder 1 , Sascha Jakob, Kerstin Kunze, Tanja Maresch, Christian Calles, Jean Krutmann, Judith Haendeler * Molecular Cell & Aging Research, IUF (Institut fuer Umweltmedizinische Forschung) at the University of Duesseldorf gGmbH, Auf‘m Hennekamp 50, 40225 Duesseldorf, Germany article info Article history: Received 8 January 2008 Received in revised form 3 April 2008 Accepted 14 April 2008 Available online 22 April 2008 Keywords: Aging Thioredoxin-1 UV light Infrared Metalloproteinase-1 Collagen abstract Exposure of human skin to solar radiation, which includes ultraviolet (UV) radiation (UVA and UVB) vis- ible light and infrared radiation, induces skin aging. The effects of light have been attributed to irradia- tion-induced reactive oxygen species (ROS) formation, but the specific signaling pathways are not well understood. Detrimental effects of solar radiation are dermal diseases and photoaging. Exposure of cul- tured human dermal fibroblasts to UVA, UVB or IRA increased ROS formation in vitro. One important redox regulator is the oxidoreductase thioredoxin-1 (Trx). Trx is ubiquitously expressed and has anti-oxi- dative and anti-apoptotic properties. Besides its function to reduce H 2 O 2 , Trx binds to and regulates tran- scription factors. The aim of this study was to investigate whether Trx influences the regulation of MMP-1 and collagen Ia1 by UVA, UVB and IRA. We irradiated human dermal fibroblasts with UVA, UVB and IRA. UVA, UVB and IRA upregulated MMP-1 expression. Trx inhibited UVA-induced MMP-1 upregulation in a NFjB dependent manner. UVA, UVB and IRA reduced collagen Ia1 expression. Incubation with Trx inhib- ited the effects of UVB and IRA on collagen Ia1 expression. In conclusion, MMP-1 and collagen Ia1, which play important roles in aging processes, seems to be regulated by different transcriptional mechanisms and Trx can only influence distinct signaling pathways induced by UVA, UVB and probably IRA. Thus, Trx may serve as an important contributor to an ‘‘anti-aging therapeutic cocktail”. Ó 2008 Elsevier Inc. All rights reserved. 1. Introduction The skin acts as a physiological barrier protecting the organism against pathogens and chemical or physical damage. Aside from this important function, the skin shows age spots or wrinkles and signs of photoaging at the sun-exposed sites. It has become apparent that chronic sun exposure not only accelerates the forma- tion of age spots and wrinkles, but also has various effects on skin function. Photoaging as a result of chronic sun exposure is charac- terized by dermal connective tissue changes, which give the skin a yellowish hue and leathery consistency. Histopathological studies of photodamaged skin have revealed reduced amounts of collagen and increased expression and activity of matrix metalloproteinases (MMPs). Further studies on the degradation system of collagen have shown that aging and irradiation accelerate the degradation of extracellular matrix, demonstrating a decrease in dermal colla- gen and an increase in the matrix metalloproteinase-1 (MMP-1) expression level, which cleaves interstitial collagen, associated with aging (Fligiel et al., 2003; Jenkins, 2002). One major signaling pathway, which contributes to photoaging, is the formation of reactive oxygen species (ROS) (Jenkins, 2002). UV (UVA and UVB) irradiation and infrared A (IRA) induce ROS formation in dermal fibroblasts (Russo and Halliday, 2006; Schroeder et al., 2007a). Der- mal fibroblasts can be protected against the adverse effects of UVA, UVB and IRA irradiation by a number of both enzymatic and non- enzymatic anti-oxidants (Yan et al., 2005; Russo and Halliday, 2006; Schroeder et al., 2007a). The endogenous anti-oxidant capac- ity of the skin is a major determinant in its response to oxidative stress-mediated damage. Thus, anti-oxidants constitute an impor- tant group probably capable of preventing the occurrence and reducing the severity of irradiation-induced skin diseases and photoaging. One of the molecules, which is highly regulated by changes of the redox status in cells, is the oxidoreductase thiore- doxin-1 (Trx). Trx is a 12-kDa protein, which is ubiquitously ex- pressed in mammalian cells (Holmgren, 1989) and exerts its enzymatic activity as an oxidoreductase via cysteines 32 and 35 in the active site (Holmgren, 1989; Martin, 1995). Besides its well described function as an oxidoreductase, Trx exerts several other functions. By binding to different proteins, it modulates their func- tion: Inhibition of binding to the apoptosis signaling kinase 1 and to the transcription factors AP1, Ref1 and NFjB modulates the abil- ity of Trx to regulate cellular functions (Liu et al., 2000; Tanaka 0531-5565/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.exger.2008.04.009 * Corresponding author. Tel.: +49 211 3389 291; fax: +49 211 3389 331. E-mail address: juhae001@uni-duesseldorf.de (J. Haendeler). 1 These authors contributed equally to the work. Experimental Gerontology 43 (2008) 633–637 Contents lists available at ScienceDirect Experimental Gerontology journal homepage: www.elsevier.com/locate/expgero