hide
Free keywords:
ULTRAVIOLET-B IRRADIATION; GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE-C;
SKIN; ISOFLAVONES; ACTIVATION; CELLSDermatology; 3D culture; 7, 8, 4-trihydroxyisoflavone; matrix metalloproteinase-1;
Protein kinase C iota;
Abstract:
The soy isoflavone daidzein is bioconverted to 7,8,4-trihydroxyisoflavone (7,8,4-THIF) by microorganisms. Here, we investigated the matrix metalloproteinase (MMP)-1 inhibitory properties of 7,8,4-THIF that arise through the suppression of UVB-induced MMP-1 expression. 7,8,4-THIF reduced UVB-induced MMP-1 expression at the transcriptional level in primary human dermal fibroblasts and inhibited UVB-induced transcriptional activity of AP-1, a major activator of MMP-1 expression. Additionally, it was observed that the mitogen-activated protein kinase (MAPK) pathway, a crucial signalling cascade for MMP-1 expression, was suppressed by 7,8,4-THIF. Protein kinase C iota (PKC) was suspected to be a direct target of 7,8,4-THIF. The direct interaction between 7,8,4-THIF and PKC was confirmed using pull-down assays and immobilized metal ion affinity-based fluorescence polarization assays. Finally, we observed that 7,8,4-THIF inhibited UVB-induced MMP-1 expression in a human skin equivalent model. Taken together, these results suggest that 7,8,4-THIF, a bioconversion product of daidzein, suppresses UVB-induced MMP-1 expression.
