title: UVA-activated synthesis of metalloproteinases 1, 3 and 9 is prevented by a broad-spectrum sunscreen.
abstract: BACKGROUND
  Specific sunscreens against ultraviolet (UV) A and B radiations are essential to prevent matrix degradation and the activation of intracellular signaling pathways involved in photoaging and photocarcinogenesis. Matrix degradation results from UVA-induced production of matrix metalloproteinases (MMP) and activation of intracellular pathways in fibroblasts and keratinocytes. In particular, in keratinocytes, UVA radiation induces β-catenin nuclear translocation and stimulates MMP gene transcription. Our study was aimed at assessing the efficacy of a specific broad-spectrum sunscreen in preventing β-catenin translocation and MMPs enhanced expression in cultured keratinocytes after UVA irradiation.
  
  
  METHODS
  Sunscreen or the vehicle was spread on quartz sheet. Irradiation of HaCaT cells with 6 J/cm(2) UVA was performed through the sheet, and cells were collected for β-catenin immunostaining then visualization by confocal microscopy, and quantitative real-time polymerase chain reaction analysis of MMP-1, -3 and -9 gene expression.
  
  
  RESULTS
  As shown by immunostaining and confocal microscopy, the sunscreen abrogated UVA-induced beta-catenin translocation to the nucleus, in comparison with control groups. MMP-1, -3 and -9 mRNA expression was enhanced by 7, 7 and 4 folds (P < 0.0001, P < 0.001 and P < 0.01, respectively) in unprotected UVA-irradiated cells compared to the non-irradiated control. Sunscreen protection of the cells significantly reduced UVA-induced expression of MMP-1, -3 and -9 by 83% (P < 0.01), 80% (P < 0.01) and 65% (P < 0.05), respectively.
  
  
  CONCLUSIONS
  This study demonstrated the efficacy of this broad-spectrum sunscreen in preventing UVA-induced effects on the markers of photoaging and photocarcinogenesis in vitro. It was able to protect HaCaT keratinocytes from UVA-induced β-catenin translocation to the nucleus and MMPs expression.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, CHU Purpan, Toulouse, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Jean
authors.forename: Patrick
authors.initials: P
authors.lastname: Bogdanowicz
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Haure
authors.forename: Nathalie
authors.initials: N
authors.lastname: Castex-Rizzi
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
authors.forename: Guy
authors.initials: G
authors.lastname: Laurent
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology* / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D013473:Sunscreening Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D013473:Sunscreening Agents; D051176:beta Catenin; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1