Increased expression of SMAD6 contributes to photoaging via suppression of TGF-β signaling pathway

Summary: Abstract Body: Photoaging is a skin aging symptom caused by chronic ultraviolet (UV) exposure and it remains a significant unresolved issue. In the dermis of photoaged skin, a decrease or degeneration of elastic fiber is typically observed, contributing to reduced skin elasticity. TGF-β signaling is known to regulate elastin expression, but the effects of long-term exposure to UV on the molecules that mediate this signaling are not completely clear. In this study, we collected sun-protected skins from young and elderly subjects, as well as sun-exposed skin from the elderly ones, for immunohistological analysis. We found that the expression of SMAD6, an inhibitory factor of TGF-β signaling, was increased in dermal fibroblasts of the sun-exposed skin of the elderly subjects compared to the sun-protected skin of the young ones. Based on this finding, we screened plant extracts that inhibit SMAD6 expression using cultured fibroblasts, aiming to develop a new cosmetic technology for anti-photoaging care. Consequently, Geranium thunbergii extract suppressed SMAD6 expression and increased elastin, fibrillin-1 gene expression, and elastic fiber formation. These results suggest that SMAD6 is a novel factor involved in photoaging via suppression of TGF-β signaling and inhibition of SMAD6 by botanical extracts could be a promising strategy to prevent and/or improve photoaging. Keita Sato¹, Kei Takano¹, Mika Aoki¹, Masayoshi Ikeuchi¹, Masatoshi Kondou¹, Shinya Kasamatsu¹, Yoshito Takahashi¹ 1. Biological Science Research, Kao Kabushiki Kaisha Odawara Kenkyujo, Odawara, Kanagawa Prefecture, Japan. UV Biology/Injury and Non-melanoma Cancers