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Papers In Press, published online ahead of print June 1, 2005
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Dermatology Dept., Seoul National University College of Medicine, Seoul 110-744
Corresponding Author: falco72{at}hanmail.net
UV radiation 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 effects of eicosapentaenoic acid (EPA), a dietary w-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 ERK and JNK activation, but not by p38 activation. Pretreating HDFs with EPA inhibited UV-induced MMP-1 expression in a dose-dependent manner, and also inhibited the UV-induced activations of ERK and JNK by inhibiting MEK1 and SEK1 activation, respectively. Moreover, these decreased activations of ERK and JNK by EPA resulted in the inhibition of c-Fos expression and c-Jun expression/phosphorylation induced by UV, respectively, which led to the inhibition of UV-induced AP-1 DNA binding activity. Moreover, this inhibitory effect of EPA on MMP-1 was not mediated by an antioxidant effect. We also found that EPA inhibited TPA- or TNF-a-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. Thus, indicating that EPA is a potential agent for the prevention and treatment of skin aging.
Revised on May 18, 2005
Accepted on May 24, 2005
Eicosapentaenoic acid (EPA) inhibits UV-induced MMP-1 expression in human dermal fibroblasts
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