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.
Highlights
Ultraviolet (UV) irradiation regulates UV-responsive genes, including matrix metalloproteinases (MMPs)
To investigate the roles of mitogen-activated protein kinase (MAPK) in UV-induced matrix metalloproteinase-1 (MMP-1) expression, human dermal fibroblast (HDF) were pretreated with U0126 (10 M; a MAP or ERK kinase (MEK1)-specific inhibitor), SP600125 (25 M; a Jun-N-terminal kinase (JNK)-specific inhibitor), or SB203580 (10 M; a p38-specific inhibitor) for 30 min and irradiated with UV (75 mJ/cm2)
These results suggest that the activation of the p44 and p42 MAP kinase (ERK) and JNK pathways mediates UV-induced MMP-1 expression in cultured HDFs
Summary
Ultraviolet (UV) irradiation regulates UV-responsive genes, including matrix metalloproteinases (MMPs). 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. The expression of various ultraviolet (UV)-induced MMPs in dermal fibroblasts leads to the breakdown of collagen and other extracellular matrix proteins and is related to photoaging in human skin [5, 8, 9]. Fisher and Voorhees [8] suggested that UV radiation activates growth factor receptors, which induce the activation of protein kinase cascades, such as the mitogen-activated protein kinase (MAPK) cascade This activation is succeeded by an increase in the expression of c-Jun and c-Fos, which form the activator protein-1 (AP-1) complex.
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