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Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts
Cited 90 time in
Web of Science
Cited 94 time in Scopus
- Authors
- Issue Date
- 2005-06-03
- Citation
- J Lipid Res. 2005 Aug;46(8):1712-20. Epub 2005 Jun 1.
- Keywords
- Cells, Cultured ; Eicosapentaenoic Acid/*pharmacology ; Fatty Acids, Omega-3/pharmacology ; Fibroblasts/*metabolism ; Gene Expression Regulation/drug effects/*radiation effects ; Humans ; JNK Mitogen-Activated Protein Kinases/metabolism ; Matrix Metalloproteinase 1/*genetics ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Signal Transduction ; Skin/cytology ; Ultraviolet Rays
- Abstract
- Ultraviolet (UV) irradiation regulates UV-responsive genes, including matrix metalloproteinases (MMPs). Moreover, UV-induced MMPs cause connective tissue damage and the skin to become wrinkled and aged. Here, we investigated the effect of eicosapentaenoic acid (EPA), a dietary omega-3 fatty acid, on UV-induced MMP-1 expression in human dermal fibroblasts (HDFs). We found that UV radiation increases MMP-1 expression and that this is mediated by p44 and p42 MAP kinase (ERK) and Jun-N-terminal kinase (JNK) activation but not by p38 activation. Pretreatment of HDFs with EPA inhibited UV-induced MMP-1 expression in a dose-dependent manner and also inhibited the UV-induced activation of ERK and JNK by inhibiting ERK kinase (MEK1) and SAPK/ERK kinase 1 (SEK1) activation, respectively. Moreover, inhibition of ERK and JNK by EPA resulted in the decrease of c-Fos expression and c-Jun phosphorylation/expression induced by UV, respectively, which led to the inhibition of UV-induced activator protein-1 DNA binding activity. This inhibitory effect of EPA on MMP-1 was not mediated by an antioxidant effect. We also found that EPA inhibited 12-O-tetradecanoylphorbol-13-acetate- or tumor necrosis factor-alpha-induced MMP-1 expression in HDFs and UV-induced MMP-1 expression in HaCaT cells. In conclusion, our results demonstrate that EPA can inhibit UV-induced MMP-1 expression by inhibiting the MEK1/ERK/c-Fos and SEK1/JNK/c-Jun pathways. Therefore, EPA is a potential agent for the prevention and treatment of skin aging.
- ISSN
- 0022-2275 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15930517
https://hdl.handle.net/10371/22626
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