243 Permeability and immune barrier differences of healthy human skin

Abstract

Adiponectin enhances human keratinocyte lipid synthesis via SIRT1 and nuclear hormone receptor signaling. In an effort to put adiponectin signaling into practical use for the improvement of skin barrier function, the effects of a newly synthesized adiponectin-derived peptide (Adi-pep D) on keratinocyte lipid synthesis and differentiation were evaluated in vitro and in vivo. Adi-pep D induced adiponectin receptor activity by receptor-mediated endocytosis in HaCaT cells Further, in Adi-pep D-treated primary human keratinocytes, Adi-pep D increased the expression of the lipid synthesis enzymes HMG CoA reductase and serinepalmitoyl transferase mRNA as well as the lipid transporter ABCA12, which is related to the homeostasis of skin barrier function. The expression levels of the transcription factors SIRT1, LXRa, and SREBP also increased. Nile red fluorescence staining showed an increase in the neutral lipid content in Adi-pep-treated keratinocytes. Adi-pep D also increased the expression of epidermal differentiation marker proteins (e.g., filaggrin, involucrin, and loricrin) in HaCaT cells. We further evaluated whether the synthetic peptide can reduce the deterioration of barrier function by the topical application of a highly potent corticosteroid on murine skin. Functionally, the basal transepidermal waterloss and stratum corneum hydration levels were not different but the barrier recovery rate and integrity tended to be better than those of the non-treated skin. When the epidermis was observed by transmission electron microscopy, the count and secretion of the lamellar body in the stratum corneum-granulosa interface were significantly increased. These results suggest that the newly synthesized Adi-pep can improve lipid synthesis, differentiation, and the recovery of skin barrier function.