title: The effects of Musk T on peroxisome proliferator-activated receptor [PPAR]-alpha activation, epidermal skin homeostasis and dermal hyaluronic acid synthesis.
abstract: Peroxisome proliferators activated receptors (PPARs) are a family of nuclear hormone receptors that heterodimer with the retinoid X receptor and function as transcriptional regulators of genes. Topically Applied PPAR-alpha agonists possess receptor mediated, pro-differentiating/anti-proliferative effects, lipid metabolism stimulation, and anti-inflammatory activity, which suggest that they could be beneficial for the treatment of a variety of cutaneous diseases. Hyaluronan (HA), a high-molecular-weight linear glycosaminoglycan consisting of alternating D: -glucuronic acid and N-acetyl-D: -glucosamine residues, is one of the major extracellular matrix components in skin. Among the family of HA synthase genes (HAS1, 2, 3) so far identified, one group has demonstrated that the expressions of HAS2 and HAS3 play crucial roles in the regulation of HA synthesis in human skin fibroblasts and keratinocytes, respectively, but the precise regulatory mechanisms are still unknown. We examine Musk T called Ethylene brassylate, Astratone or 1,4-Dioxacycloheptadecane-5,17-dione, which used as just a perfume ingredient, plays a role as PPAR-alpha ligand in vitro and stimulates skin barrier recovery, ceramide synthesis, beta-Glucocerebrosidase, involucrin expression in epidermis in vivo; and examine that Musk T stimulates HAS expression and HA synthesis in human skin fibroblast. Through these experiments, we conclude that Musk T is PPAR-alpha ligand, effects on keratinocyte differentiation, intercellular lipid synthesis in epidermis, HA synthesis stimulation in dermis.
authors.affiliation: Safety and Efficacy Research, Skin Research Institute, Amorepacific Corporation/R&D Center, Yongin, South Korea. shkim1228@amorepacific.com
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Kim
authors.forename: Gae Won
authors.initials: GW
authors.lastname: Nam
authors.forename: Hae Kwang
authors.initials: HK
authors.lastname: Lee
authors.forename: Seong Joon
authors.initials: SJ
authors.lastname: Moon
authors.forename: Ih Seop
authors.initials: IS
authors.lastname: Chang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D000091344:Filaggrin Proteins; D014453:Glucuronosyltransferase / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D047493:PPAR alpha / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D004988:Ethers, Cyclic; D005229:Fatty Acids, Monounsaturated; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D047493:PPAR alpha; D011498:Protein Precursors; D012333:RNA, Messenger; C008563:musk; C032253:involucrin; D006820:Hyaluronic Acid; C519611:ethylene brassylate; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases