PKCɩ is a molecular target suppressing UVB-induced MMP-1 expression by 7,8,4-trihydroxyisoflavone in human dermal fibroblasts

Abstract

Abnormal matrix metalloproteinase-1 (MMP-1) is a representative mediator in photoaging which degrades collagen in human skin tissue. Solar UV induces the activation of various inflammatory signaling pathways such as mitogen-activated protein kinases (MAPKs) and consequently MMP-1 expression. In this paper, 7,8,4-trihydroxyisoflavone (7,8,4-THIF), a metabolite of daidzin in soy is suggested to be a possible anti-photoaging agent. 7,8,4-THIF reduces UVB-induced MMP-1 expression in transcriptional level in human dermal fibroblasts. The effect of 7,8,4-THIF on UVB-induced MAPKs signaling pathway is evaluated. 7,8,4-THIF decreases UVB-induced phosphorylation of MEK, MKK4, and MKK3/6 as well as ERK, JNK, and p38. Based on Kinase profiling analysis, protein kinase C iota (PKCι) is suggested as a direct target of 7,8,4-THIF. In addition, pull-down assay shows that 7,8,4-THIF directly binds PKCι competitively with ATP. In results, 7,8,4-THIF produces the anti-photoaging effect by directly targeting PKCι in human dermal fibroblasts and suppressing UVB-induced MMP-1 expression. Thus, 7,8,4-THIF could be beneficial agent for reducing UV-induced wrinkle formation.