title: Hyaluronan tetrasaccharides stimulate ceramide production through upregulated mRNA expression of ceramide synthesis-associated enzymes.
abstract: It has been reported that hyaluronan has different physiological functions as suggested by variation in molecular weight. In addition, it has also been reported that CD44, the major hyaluronan receptor, was demonstrated to induce keratinocyte differentiation and lipid synthesis of cholesterol. We focus attention on the hyaluronan tetrasaccharides (HA4) which is the smallest unit of hyaluronan. We previously reported that HA4 induced keratinocyte differentiation and that CD44 may be involved. For the purpose of clarifying the influence of HA4 on ceramide synthesis, we evaluated both of these factors in keratinocytes in vitro and in vivo. The mRNA expression of ceramide synthesis-associated enzymes and intracellular ceramide content were evaluated after HA4 treatment in normal human epidermal keratinocytes. In addition, the ceramide increasing effect of HA4 on skin in UVA-irradiated hairless mice was assessed by water content of stratum corneum (SC) and transepidermal water loss (TEWL) methods. The mRNA expression of ceramide synthesis-associated enzymes and intracellular ceramide content after HA4 treatment were increased compared with the control. Furthermore, HA4 treatment increased water content of SC and decreased TEWL. These findings suggest that HA4 affected ceramide synthesis and is involved in the improvement of UV-induced skin damage.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Kage
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan. tokudome@josai.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tokudome
mesh_terms: D000818:Animals; D002460:Cell Line; D002518:Ceramides / Q000096:biosynthesis / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D009844:Oligosaccharides / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects; D015854:Up-Regulation / Q000187:drug effects; D014867:Water / Q000378:metabolism*
chemical_list: D002518:Ceramides; D009844:Oligosaccharides; D012333:RNA, Messenger; D014867:Water; D006820:Hyaluronic Acid
keywords: Ceramide synthesis; Hyaluronan oligosaccharide; Skin damage