The effect of 2',4',7-trihydroxyisoflavone on ultraviolet-induced matrix metalloproteinases-1 expression in human skin fibroblasts.

Author: Moon HI, Chung JH

Author affiliation: Molecular Neuroscience and Vascular Biology Laboratory, Department of Surgery, University of Kentucky Medical Center, Lexington, KY 40536, USA. himoon2@uky.edu

Publication date & source: 2006.02.06, FEBS Lett., 580(3):769-74. Epub 2006 Jan 9.

Publication type: Retracted Publication

UV-induced matrix metalloproteinases (MMPs) cause connective tissue damage and the skin to become wrinkled and aged. Here, we investigated the effect of 2',4',7-trihydroxyisoflavone (THF) on UV-induced MMP-1 expression in human skin fibroblasts (HSFs). We found that UV irradiation increases MMP-1 expression and that this is mediated by ERK and JNK activation, but not by p38 activation. Pretreatment of HSFs with 2',4',7-THF 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, inhibitions of ERK and JNK by 2',4',7-THF 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 AP-1 DNA binding activity. This inhibitory effect of 2',4',7-THF on MMP-1 was not mediated by an antioxidant effect. In conclusion, our results demonstrate that 2',4',7-THF can inhibit UV-induced MMP-1 expression by inhibiting the MEK1/ERK/c-Fos and SEK1/JNK/c-Jun pathways. Therefore, 2',4',7-THF is a potential agent for the prevention and treatment of skin aging.

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