Activation of SIRT1 Enhances Epidermal Permeability Barrier Formation through Ceramide Synthase 2– and 3–Dependent Mechanisms

Abstract

We recently demonstrated that a synthetic SIRT1 activator, hexacarboxymethyldipeptide-12 (HMD-12), protects the skin against damage caused by UV irradiation (Lim et al., 2017). In addition, in one study, SIRT1 activation has been shown to promote keratinocyte (KC) differentiation, which is a critical process for the formation of the epidermal barrier, but the cellular mechanism underlying SIRT1-mediated KC differentiation has remained unknown (Blander et al., 2009). Therefore, in this study, we investigated how SIRT1 influences the regulation of epidermal permeability barrier function as well as KC differentiation using HMD-12, which has been previously shown to be a SIRT1 activator.