title: Tight control of matrix metalloproteinase-1 activity in human skin.
abstract: Chronic ultraviolet irradiation leads to photoaging in human skin, which is associated with degradation of connective tissue. This is partly due to the fibroblast collagenase (matrix metalloproteinase 1 [MMP-1]). Using complementary DNA array technique we demonstrate that after UV irradiation, MMP-1, MMP-3 and the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) are time-dependently induced on the messenger RNA level in dermal fibroblasts in vitro and in vivo in human buttock skin. This increase in gene expression is paralleled by an increase of latent and active MMP-1 protein after low-dose UV-A exposure in vitro. In vivo the concentration of latent MMP-1 in suction blister fluids peaks 24 h after irradiation with 2 minimal erythema doses of solar simulated radiation. However, only a small proportion of MMP-1 in vitro (5.5 +/- 1.5%) and in vivo is active, whereas the majority of MMP-1 remains in its inactive proform. Interestingly, in suction blister fluid the concentration and duration of TIMP-1 expression exceeds that of MMP-1. Taken together, these data indicate that MMP-1 activity is tightly regulated transcriptionally and posttranscriptionally. Furthermore, the pronounced individual differences in all targets investigated provide a possible explanation for the different susceptibility of individuals to UV exposure and, thus, to the clinical features of photodamage.
authors: Beiersdorf AG, Paul Gerson Unna Skin Research Center, Unnastr. 48, 20245 Hamburg, Germany.
authors: Kirstin M
authors: KM
authors: Südel
authors: Kirsten
authors: K
authors: Venzke
authors: Elke
authors: E
authors: Knussmann-Hartig
authors: Ingrid
authors: I
authors: Moll
authors: Franz
authors: F
authors: Stäb
authors: Horst
authors: H
authors: Wenck
authors: Klaus-Peter
authors: KP
authors: Wittern
authors: Günther
authors: G
authors: Gercken
authors: Stefan
authors: S
authors: Gallinat
mesh_terms: D004307:Dose-Response Relationship, Radiation; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012867:Skin / Q000201:enzymology / Q000528:radiation effects*; D015595:Skin Aging; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1