title: Chronic UVB-irradiation actuates perpetuated dermal matrix remodeling in female mice: Protective role of estrogen.
abstract: Chronic UVB-exposure and declined estradiol production after menopause represent important factors leading to extrinsic and intrinsic aging, respectively. Remodeling of the extracellular matrix (ECM) plays a crucial role in both responses. Whether the dermal ECM is able to recover after cessation of UVB-irradiation in dependence of estradiol is not known, however of relevance when regarding possible treatment options. Therefore, the endogenous sex hormone production was depleted by ovariectomy in female mice. Half of the mice received estradiol substitution. Mice were UVB-irradiated for 20 weeks and afterwards kept for 10 weeks without irradiation. The collagen-, hyaluronan- and proteoglycan- (versican, biglycan, lumican) matrix, collagen cleavage products and functional skin parameters were analyzed. The intrinsic aging process was characterized by increased collagen fragmentation and accumulation of biglycan. Chronic UVB-irradiation additionally augmented the lumican, versican and hyaluronan content of the dermis. In the absence of further UVB-irradiation the degradation of collagen and accumulation of biglycan in the extrinsically aged group was perpetuated in an excessive matter. Whereas estradiol increased the proteoglycan content, it reversed the effects of the perpetuated extrinsic response on collagen degradation. Suspension of the intrinsic pathway might therefore be sufficient to antagonize UVB-evoked long-term damage to the dermal ECM.
authors.affiliation: Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.|Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Röck
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Simon Andreas
authors.initials: SA
authors.lastname: Joosse
authors.affiliation: Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Müller
authors.affiliation: Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Heinisch
authors.affiliation: Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fuchs
authors.affiliation: Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meusch
authors.affiliation: Department of Dermatology, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Zipper
authors.affiliation: Department of Dermatology, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Reifenberger
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.affiliation: Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
authors.forename: Jens Walter
authors.initials: JW
authors.lastname: Fischer
mesh_terms: D000818:Animals; D001706:Biopsy; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D020405:Dermis / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006820:Hyaluronic Acid / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D008812:Mice, Hairless; D010052:Ovariectomy; D020011:Protective Agents / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004967:Estrogens; D020011:Protective Agents; D011509:Proteoglycans; D006820:Hyaluronic Acid; D003094:Collagen