The effect of 2',4',7-trihydroxyisoflavone on ultraviolet-induced matrix metalloproteinases-1 expression in human skin fibroblasts.
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.
Moon
Hyung-In
HI
Molecular Neuroscience and Vascular Biology Laboratory, Department of Surgery, University of Kentucky Medical Center, Lexington, KY 40536, USA. himoon2@uky.edu
Chung
Jin Ho
JH
D000375:Aging / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000201:enzymology* / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D004791:Enzyme Inhibitors; D007529:Isoflavones; D018808:Transcription Factor AP-1; C506346:2',4',7-trihydroxyisoflavone; D011505:Protein-Tyrosine Kinases; D020781:Matrix Metalloproteinase 1